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Sample records for 5-km time trial

  1. The effect of skin temperature on performance during a 7.5-km cycling time trial.

    PubMed

    Levels, Koen; de Koning, Jos J; Foster, Carl; Daanen, Hein A M

    2012-09-01

    Aerobic exercise performance is seriously compromised in the heat. Possibly, a high skin temperature causes a rating of perceived exertion (RPE)-mediated decrease in exercise intensity. The purpose of this study was to determine the effect of skin temperature on power output during a 7.5-km cycling time trial. Thirteen well-trained male subjects performed a 7.5-km cycling time trial at 15°C and 50% relative humidity (CONTROL), with radiative heat stress during the time trial, and with (PRECOOL) or without (HEAT) precooling. Heat stress was applied by infrared heaters positioned in front of the cycle ergometer between 1.5 and 6.0 km. Skin, rectal, and pill temperature, power output, heart rate, and RPE were measured during the trial. Despite the lower mean skin temperature at the start of the time trial for PRECOOL compared to HEAT (-2.1 ± 0.7°C; P < 0.01) and CONTROL (-1.8 ± 0.6°C; P < 0.05), and a greater increase in mean skin temperature during the heat stress period for PRECOOL (4.5 ± 1.0°C) and HEAT (3.9 ± 0.8°C) than for CONTROL (-0.3 ± 0.6°C; P < 0.01), no differences in power output were found between HEAT (273 ± 45 W) and CONTROL (284 ± 43 W; P = 0.11) and between HEAT and PRECOOL (266 ± 50 W; P = 0.47). Power output during the time trial was greater for CONTROL than for PRECOOL (P < 0.05). Additionally, no differences were observed in core temperature measures, HR, and RPE. Skin temperature does not affect the selection and modulation of exercise intensity in a 7.5-km cycling time trial.

  2. Effect of Practical Precooling on Neuromuscular Function and 5-km Time-Trial Performance in Hot, Humid Conditions Among Well-Trained Male Runners.

    PubMed

    Randall, Carla A; Ross, Emma Z; Maxwell, Neil S

    2015-07-01

    This study investigated whether torso and thigh precooling during a warm-up effects neuromuscular function and 5-km time-trial performance in hot, humid conditions. Eight well-trained male runners completed 3 randomized time-trials in 32.2 ± 0.8° C and 48.6 ± 6.7% relative humidity. A 30-minute warm-up was completed with no cooling (Control), precooling by an ice vest (Vest), or ice packs covering the thighs (Packs). Before the warm-up and after the time-trial, supramaximal femoral nerve stimulation was delivered during and following maximal isometric contractions. Core and skin temperature, heart rate, and perceptual ratings were recorded before and during the warm-up and time-trial. Overall performance time was improved in Packs compared with Control (1,407 ± 80 seconds vs. 1,492 ± 88 seconds; p ≤ 0.05) but not in Vest (1,444 ± 71 seconds; p > 0.05). In Packs, a higher exercise intensity (p ≤ 0.05) and less cumulative time (p < 0.01) were evident during the last kilometer compared with Control. Maximum voluntary force, voluntary activation, muscle contractility, and membrane excitability were not different after exercise or between conditions. Ten minutes after the warm-up, skin temperature was lower in Vest and Packs compared with Control (p < 0.01). Thermal strain and body heat content change was lower in Vest and Packs, respectively (p ≤ 0.05). Findings indicate that torso and thigh precooling during a warm-up reduces thermoregulatory strain. However, thigh opposed to torso precooling provides greater performance improvements. Neuromuscular function did not aid performance, indicating that transient changes in afferent feedback and muscle recruitment may enhance endurance trial performance.

  3. Effect of Practical Precooling on Neuromuscular Function and 5-km Time-Trial Performance in Hot, Humid Conditions Among Well-Trained Male Runners.

    PubMed

    Randall, Carla A; Ross, Emma Z; Maxwell, Neil S

    2015-07-01

    This study investigated whether torso and thigh precooling during a warm-up effects neuromuscular function and 5-km time-trial performance in hot, humid conditions. Eight well-trained male runners completed 3 randomized time-trials in 32.2 ± 0.8° C and 48.6 ± 6.7% relative humidity. A 30-minute warm-up was completed with no cooling (Control), precooling by an ice vest (Vest), or ice packs covering the thighs (Packs). Before the warm-up and after the time-trial, supramaximal femoral nerve stimulation was delivered during and following maximal isometric contractions. Core and skin temperature, heart rate, and perceptual ratings were recorded before and during the warm-up and time-trial. Overall performance time was improved in Packs compared with Control (1,407 ± 80 seconds vs. 1,492 ± 88 seconds; p ≤ 0.05) but not in Vest (1,444 ± 71 seconds; p > 0.05). In Packs, a higher exercise intensity (p ≤ 0.05) and less cumulative time (p < 0.01) were evident during the last kilometer compared with Control. Maximum voluntary force, voluntary activation, muscle contractility, and membrane excitability were not different after exercise or between conditions. Ten minutes after the warm-up, skin temperature was lower in Vest and Packs compared with Control (p < 0.01). Thermal strain and body heat content change was lower in Vest and Packs, respectively (p ≤ 0.05). Findings indicate that torso and thigh precooling during a warm-up reduces thermoregulatory strain. However, thigh opposed to torso precooling provides greater performance improvements. Neuromuscular function did not aid performance, indicating that transient changes in afferent feedback and muscle recruitment may enhance endurance trial performance. PMID:26102259

  4. SDM transmission of real-time 10GbE traffic using commercial SFP + transceivers over 0.5km elliptical-core few-mode fiber.

    PubMed

    Ip, Ezra; Milione, Giovanni; Li, Ming-Jun; Cvijetic, Neda; Kanonakis, Konstantinos; Stone, Jeffery; Peng, Gaozhu; Prieto, Xesús; Montero, Carlos; Moreno, Vicente; Liñares, Jesús

    2015-06-29

    We experimentally demonstrate the first few-mode space division multiplexed (SDM) transmission of real-time 10Gb/s Ethernet (10GbE) traffic using commercial small form-factor pluggable SFP + transceivers without coherent detection or multiple input multiple output digital signal processing (MIMO-DSP) over 0.5km elliptical-core few-mode-fiber, achieving <-26dB crosstalk between LP(11e) and LP(11o) modes at 1.3μm. PMID:26191720

  5. Time-temperature-burial significance of Devonian anthracite implies former great (approx. 6. 5 km) depth of burial of Catskill Mountains, New York

    SciTech Connect

    Friedman, G.M.; Sanders, J.E.

    1982-02-01

    Specimens of coalified plant debris in Tully-correlative strata of the Gilboa Formation (uppermost Middle Devonian) within the eastern Catskill Mountains of New York State have been converted to anthracite having a vitrinite reflectance of 2.5%. This implies a level of organic metamorphism (LOM) of 16. The specimens are about 350 m.y. old; if 200 m.y. is taken as the duration of the time of exposure to the maximum geothermal temperature, then the LOM of 16 and other thermal indicators imply a maximum temperature of 190/sup 0/C. Using a geothermal gradient of 26/sup 0/C.km/sup -1/ (17/sup 0/F.1,000 ft/sup -1/), a former depth of burial of 6.5 km is implied. Such former deep burial is not usually inferred for the Catskills, but it is consistent with the idea that the thick (about 6.4 km or 21,000 ft) Carboniferous strata of northeastern Pennsylvania formerly extended northeast far enough to bury the Catskills. The lack of metamorphism of the Paleozoic strata lying about 4.5 km beneath the Tully-correlative rocks and exposed in the adjacent Hudson Valley places low limits on the former geothermal gradient; this supports the concept of great depth of former burial of the Catskills. For example, 6.5 km of former burial and a geothermal gradient of 26/sup 0/C.km/sup -1/ imply a temperature of 307/sup 0/C for the base of the Paleozoic. By contrast, only 1 km of former burial requires a geothermal gradient of 170/sup 0/C.km/sup -1/, which would have subjected the base of the Paleozoic to a temperature of 955/sup 0/GAMMA, which is far higher than the 600 to 650/sup 0/C recently inferred for the Acadian-age metamorphism of the Taconic allochthon in southwestern Massachusetts and adjoining areas.

  6. Time-temperature-burial significance of Devonian anthracite implies former great (˜6.5 km) depth of burial of Catskill Mountains, New York

    NASA Astrophysics Data System (ADS)

    Friedman, Gerald M.; Sanders, John E.

    1982-02-01

    Specimens of coalified plant debris in Tully-correlative strata of the Gilboa Formation (uppermost Middle Devonian) within the eastern Cat-skill Mountains of New York State have been converted to anthracite having a vitrinite reflectance of 2.5%. This implies a level of organic metamorphism (LOM) of 16. A similar degree of thermal activity is implied by the black color (Staplin kerogen-alteration index of 4) of the associated (possibly recycled) carbonized kerogen, a conodont-alteration index of 4, and authigenic chlorite and local sericite fillings of the former interparticle pores of interbedded sandstones. The specimens are about 350 m.y. old; if 200 m.y. is taken as the duration of the time of exposure to the maximum geothermal temperature, then the LOM of 16 and other thermal indicators imply a maximum temperature of 190 °C. Using a geothermal gradient of 26 °C · km-1 (17 °F · 1,000 ft-1), a former depth of burial of 6.5 km is implied. Such former deep burial is not usually inferred for the Catskills, but it is consistent with the idea that the thick (about 6.4 km or 21,000 ft) Carboniferous strata of northeastern Pennsylvania formerly extended northeast far enough to bury the Catskills. The lack of metamorphism of the Paleozoic strata lying about 4.5 km beneath the Tully-correlative rocks and exposed in the adjacent Hudson Valley places low limits on the former geothermal gradient; this supports the concept of great depth of former burial of the Catskills. For example, 6.5 km of former burial and a geothermal gradient of 26 °C · km-1 imply a temperature of 307 °C for the base of the Paleozoic. By contrast, only 1 km of former burial requires a geothermal gradient of 170 °C · km-1, which would have subjected the base of the Paleozoic to a temperature of 955 °C, which is far higher than the 600 to 650 °C recently inferred for the Acadian-age metamorphism of the Taconic allochthon in southwestern Massachusetts and adjoining areas.

  7. Acute Impact of Inhaled Short Acting B2-Agonists on 5 Km Running Performance

    PubMed Central

    Dickinson, John; Hu, Jiu; Chester, Neil; Loosemore, Mike; Whyte, Greg

    2014-01-01

    Whilst there appears to be no ergogenic effect from inhaled salbutamol no study has investigated the impact of the acute inhalation of 1600 µg, the World Anti-Doping Agency (WADA) daily upper limit, on endurance running performance. To investigate the ergogenic effect of an acute inhalation of short acting β2-agonists at doses up to 1600 µg on 5 km time trial performance and resultant urine concentration. Seven male non-asthmatic runners (mean ± SD; age 22.4 ± 4.3 years; height 1.80 ± 0.07 m; body mass 76.6 ± 8.6 kg) provided written informed consent. Participants completed six 5 km time-trials on separate days (three at 18 °C and three at 30 °C). Fifteen minutes prior to the initiation of each 5 km time-trial participants inhaled: placebo (PLA), 800 µg salbutamol (SAL800) or 1600 µg salbutamol (SAL1600). During each 5 km time-trial HR, VO2, VCO2, VE, RPE and blood lactate were measured. Urine samples (90 ml) were collected between 30-180 minutes post 5 km time-trial and analysed for salbutamol concentration. There was no significant difference in total 5 km time between treatments (PLA 1714.7 ± 186.2 s; SAL800 1683.3 ± 179.7 s; SAL1600 1683.6 ± 190.7 s). Post 5 km time-trial salbutamol urine concentration between SAL800 (122.96 ± 69.22 ug·ml-1) and SAL1600 (574.06 ± 448.17 ug·ml-1) were not significantly different. There was no improvement in 5 km time-trial performance following the inhalation of up to 1600 µg of salbutamol in non-asthmatic athletes. This would suggest that the current WADA guidelines, which allow athletes to inhale up to 1600 µg per day, is sufficient to avoid pharmaceutical induced performance enhancement. Key points Inhaling up to 1600 µg of Salbutamol does not result in improved 5 km time trial performance. The position of Salbutamol on the World Anti-Doping Agency list of prohibited appears justified. Athletes who use up to 1600 µg Salbutamol in one day need to review their therapy as it would suggest their respiratory

  8. How does music aid 5 km of running?

    PubMed

    Bigliassi, Marcelo; León-Domínguez, Umberto; Buzzachera, Cosme F; Barreto-Silva, Vinícius; Altimari, Leandro R

    2015-02-01

    This research investigated the effects of music and its time of application on a 5-km run. Fifteen well-trained male long-distance runners (24.87 ± 2.47 years; 78.87 ± 10.57 kg; 178 ± 07 cm) participated in this study. Five randomized experimental conditions during a 5-km run on an official track were tested (PM: motivational songs, applied before 5 km of running; SM: slow motivational songs, applied during 5 km of running; FM: fast and motivational songs, applied during 5 km of running; CS: calm songs, applied after 5 km of running; CO: control condition). Psychophysiological assessments were performed before (functional near-infrared spectroscopy, heart rate variability [HRV], valence, and arousal), during (performance time, heart rate, and rate of perceived exertion [RPE]), and after (mood, RPE, and HRV) tests. The chosen songs were considered pleasurable and capable of activating. Furthermore, they activated the 3 assessed prefrontal cortex (PFC) areas (medial, right dorsolateral, and left dorsolateral) similarly, generating positive emotional consequences by autonomous system analysis. The first 800 m was accomplished faster for SM and FM compared with other conditions (p ≤ 0.05); moreover, there was a high probability of improving running performance when music was applied (SM: 89%; FM: 85%; PM: 39%). Finally, music was capable of accelerating vagal tonus after 5 km of running with CS (p ≤ 0.05). In conclusion, music was able to activate the PFC area, minimize perceptions, improve performance, and accelerate recovery during 5 km of running.

  9. How does music aid 5 km of running?

    PubMed

    Bigliassi, Marcelo; León-Domínguez, Umberto; Buzzachera, Cosme F; Barreto-Silva, Vinícius; Altimari, Leandro R

    2015-02-01

    This research investigated the effects of music and its time of application on a 5-km run. Fifteen well-trained male long-distance runners (24.87 ± 2.47 years; 78.87 ± 10.57 kg; 178 ± 07 cm) participated in this study. Five randomized experimental conditions during a 5-km run on an official track were tested (PM: motivational songs, applied before 5 km of running; SM: slow motivational songs, applied during 5 km of running; FM: fast and motivational songs, applied during 5 km of running; CS: calm songs, applied after 5 km of running; CO: control condition). Psychophysiological assessments were performed before (functional near-infrared spectroscopy, heart rate variability [HRV], valence, and arousal), during (performance time, heart rate, and rate of perceived exertion [RPE]), and after (mood, RPE, and HRV) tests. The chosen songs were considered pleasurable and capable of activating. Furthermore, they activated the 3 assessed prefrontal cortex (PFC) areas (medial, right dorsolateral, and left dorsolateral) similarly, generating positive emotional consequences by autonomous system analysis. The first 800 m was accomplished faster for SM and FM compared with other conditions (p ≤ 0.05); moreover, there was a high probability of improving running performance when music was applied (SM: 89%; FM: 85%; PM: 39%). Finally, music was capable of accelerating vagal tonus after 5 km of running with CS (p ≤ 0.05). In conclusion, music was able to activate the PFC area, minimize perceptions, improve performance, and accelerate recovery during 5 km of running. PMID:25029009

  10. Effects of a minimalist shoe on running economy and 5-km running performance.

    PubMed

    Fuller, Joel T; Thewlis, Dominic; Tsiros, Margarita D; Brown, Nicholas A T; Buckley, Jonathan D

    2016-09-01

    The purpose of this study was to determine if minimalist shoes improve time trial performance of trained distance runners and if changes in running economy, shoe mass, stride length, stride rate and footfall pattern were related to any difference in performance. Twenty-six trained runners performed three 6-min sub-maximal treadmill runs at 11, 13 and 15 km·h(-1) in minimalist and conventional shoes while running economy, stride length, stride rate and footfall pattern were assessed. They then performed a 5-km time trial. In the minimalist shoe, runners completed the trial in less time (effect size 0.20 ± 0.12), were more economical during sub-maximal running (effect size 0.33 ± 0.14) and decreased stride length (effect size 0.22 ± 0.10) and increased stride rate (effect size 0.22 ± 0.11). All but one runner ran with a rearfoot footfall in the minimalist shoe. Improvements in time trial performance were associated with improvements in running economy at 15 km·h(-1) (r = 0.58), with 79% of the improved economy accounted for by reduced shoe mass (P < 0.05). The results suggest that running in minimalist shoes improves running economy and 5-km running performance.

  11. Cooling vest worn during active warm-up improves 5-km run performance in the heat.

    PubMed

    Arngrïmsson, Sigurbjörn A; Petitt, Darby S; Stueck, Matthew G; Jorgensen, Dennis K; Cureton, Kirk J

    2004-05-01

    We investigated whether a cooling vest worn during an active warm-up enhances 5-km run time in the heat. Seventeen competitive runners (9 men, maximal oxygen uptake = 66.7 +/- 5.9 ml x kg(-1) x min(-1); 8 women, maximal oxygen uptake = 58.0 +/- 3.2 ml x kg(-1) x min(-1)) completed two simulated 5-km runs on a treadmill after a 38-min active warm-up during which they wore either a T-shirt (C) or a vest filled with ice (V) in a hot, humid environment (32 degrees C, 50% relative humidity). Wearing the cooling vest during warm-up significantly (P < 0.05) blunted increases in body temperature, heart rate (HR), and perception of thermal discomfort during warm-up compared with control. At the start of the 5-km run, esophageal, rectal, mean skin, and mean body temperatures averaged 0.3, 0.2, 1.8, and 0.4 degrees C lower; HR averaged 11 beats/min lower; and perception of thermal discomfort (5-point scale) averaged 0.6 point lower in V than C. Most of these differences were eliminated during the first 3.2 km of the run, and these variables were not different at the end. The 5-km run time was significantly lower (P < 0.05) by 13 s in V than C, with a faster pace most evident during the last two-thirds of the run. We conclude that a cooling vest worn during active warm-up by track athletes enhances 5-km run performance in the heat. Reduced thermal and cardiovascular strain and perception of thermal discomfort in the early portion of the run appear to permit a faster pace later in the run.

  12. Using Deception to Establish a Reproducible Improvement in 4-Km Cycling Time Trial Performance.

    PubMed

    Shei, R-J; Thompson, K; Chapman, R; Raglin, J; Mickleborough, T

    2016-05-01

    We investigated whether performance gains achieved with deception persisted after the deception was revealed, and whether pacing strategy changed. 14 trained cyclists completed 4 simulated 4-km time trials (TT) on a cycle ergometer comprising familiarization and baseline trials (BAS), followed by "unaware" (of deception, UAW) and "aware" (of deception, AW) trials on separate days. In the UAW trial, participants competed against an on-screen avatar set at 102% of their baseline trial mean power output (Pmean) believing it was set at 100% of BAS Pmean. 24 h prior to the AW trial, participants were informed of the deception in the UAW trial. 4 participants did not improve in the UAW trial compared to BAS. 10 participants improved time to completion (TTC) and Pmean in the UAW and AW trials compared to BAS (p<0.03) with no significant differences between UAW and AW (p=1.0). Pacing strategy (at 0.5-km intervals) and RPE responses were unchanged (p>0.05) for these participants. In summary, deception did not improve performance in all participants. However, participants whose time trial performance improved following deception could retain their performance gains once the deception was revealed, demonstrating a similar pacing strategy and RPE response.

  13. Effects of radiant heat exposure on pacing pattern during a 15-km cycling time trial.

    PubMed

    Levels, Koen; de Koning, Jos; Broekhuijzen, Iris; Zwaan, Tamara; Foster, Carl; Daanen, Hein

    2014-01-01

    The goal of this study was to investigate the effects of different durations of skin temperature manipulation on pacing patterns and performance during a 15-km cycling time trial. Nineteen well-trained men completed three 15-km cycling time trials in 18 °C and 50% relative humidity with 4.5-km (short-heat), 9.0-km (long-heat) or without (control) radiant heat exposure applied by infrared heaters after 1.5 km in the time trial. During the time trials, power output, mean skin temperature, rectal temperature, heart rate and rating of perceived exertion were assessed. The radiant heat exposure resulted in higher mean skin temperature during the time trial for short-heat (35.0 ± 0.6 °C) and long-heat (35.3 ± 0.5 °C) than for control (32.5 ± 1.0 °C; P < 0.001), whereas rectal temperature was similar (P = 0.55). The mean power output was less for short-heat (273 ± 8 W; P = 0.001) and long-heat (271 ± 9 W; P = 0.02) than for control (287 ± 7 W), but pacing patterns did not differ (P = 0.55). Heart rate was greatest in control (177 ± 9 beats · min(-1); P < 0.001), whereas the rating of perceived exertion remained similar. We concluded that a radiant heat exposure and associated higher skin temperature reduced overall performance, but did not modify pacing pattern during a 15-km cycling time trial, regardless of the duration of the exposure.

  14. Laboratory 20-km cycle time trial reproducibility.

    PubMed

    Zavorsky, G S; Murias, J M; Gow, J; Kim, D J; Poulin-Harnois, C; Kubow, S; Lands, L C

    2007-09-01

    This study evaluated the reproducibility of laboratory based 20-km time trials in well trained versus recreational cyclists. Eighteen cyclists (age = 34 +/- 8 yrs; body mass index = 23.1 +/- 2.2 kg/m (2); VO(2max) = 4.19 +/- 0.65 L/min) completed three 20-km time trials over a month on a Velotron cycle ergometer. Average power output (PO) (W), speed, and heart rate (HR) were significantly lower in the first time trial compared to the second and third time trial. The coefficients of variation (CV) between the second and third trial of the top eight performers for average PO, time to completion, and speed were 1.2 %, 0.6 %, 0.5 %, respectively, compared to 4.8 %, 2.0 %, and 2.3 % for the bottom ten. In addition, the average HR, VO(2), and percentage of VO(2max) were similar between trials. This study demonstrated that (1) a familiarization session improves the reliability of the measurements (i.e., average PO, time to completion and speed), and (2) the CV was much smaller for the best performers.

  15. The effect of breast support on upper body muscle activity during 5 km treadmill running.

    PubMed

    Milligan, Alexandra; Mills, Chris; Scurr, Joanna

    2014-12-01

    Breast support has previously been shown to influence surface EMG of the pectoralis major during running. Reductions in muscle activity have previously been associated with a reduction in energy cost, which may be advantageous for female runners. Ten female participants performed two self-paced (average pace 9 km h(-1)) 5 km treadmill runs under two breast support conditions (low and high); an additional bare-breasted 2 min run was also conducted. Surface EMG electrodes were positioned on the pectoralis major, anterior deltoid, medial deltoid, and upper trapezius, with data collected during the first 2 min of running and each kilometer interval thereafter. Reductions in peak EMG of the pectoralis major, anterior and medial deltoid were reported when participants ran in the high breast support during the initial intervals of the run (up to the second kilometer). The increased activation in the pectoralis major, anterior and medial deltoid in the low breast support may be due to increased tension within these muscles, induced by the greater breast pain experienced in the low breast support. This may be a strategy to reduce the independent breast movement causing the pain through increased muscular activation. This study further promotes the use of a high breast support during running with potential benefits for treadmill running associated with reductions in muscular demand during a 5 km run.

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

    PubMed

    Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

    2016-05-09

    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.

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

    PubMed Central

    Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

    2016-01-01

    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˙O2max: 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. PMID:27171108

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

    PubMed

    Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

    2016-01-01

    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. PMID:27171108

  19. Exercise-induced dehydration does not alter time trial or neuromuscular performance.

    PubMed

    Stewart, C J; Whyte, D G; Cannon, J; Wickham, J; Marino, F E

    2014-08-01

    This study examined the effect of exercise-induced dehydration by ~4% body mass loss on 5-km cycling time trial (TT) performance and neuromuscular drive, independent of hyperthermia. 7 active males were dehydrated on 2 occasions, separated by 7 d. Participants remained dehydrated (DEH, -3.8±0.5%) or were rehydrated (REH, 0.2±0.6%) over 2 h before completing the TT at 18-25 °C, 20-30% relative humidity. Neuromuscular function was determined before dehydration and immediately prior the TT. The TT started at the same core temperature (DEH, 37.3±0.3°C; REH, 37.0±0.2 °C (P>0.05). Neither TT performance (DEH, 7.31±1.5 min; REH, 7.10±1.3 min (P>0.05)) or % voluntary activation were affected by dehydration (DEH, 88.7±6.4%; REH, 90.6±6.1% (P>0.05)). Quadriceps peak torque was significantly elevated in both trials prior to the TT (P<0.05), while a 19% increase in the rate of potentiated peak twitch torque development (P<0.05) was observed in the DEH trial only. All other neuromuscular measures were similar between trials. Short duration TT performance and neuromuscular function are not reduced by dehydration, independent of hyperthermia.

  20. Which laboratory variable is related with time trial performance time in the Tour de France?

    PubMed Central

    Lucia, A; Hoyos, J; Perez, M; Santalla, A; Earnest, C; Chicharro, J

    2004-01-01

    Objective: To investigate the relationship between several physiological variables that can be easily obtained during cycle ergometer gradual testing (for example, peak power output (Wpeak), VO2max, or ventilatory threshold (VT)) and actual (>50 km) time trials (TT) time performance during the Tour de France. Methods: We collected data in professional cyclists from the first TT of the 1998 Tour de France (TT1, 58 km distance; n = 6 cyclists) and the first (TT2, 56.5 km; n = 5) and second TT of the 1999 Tour de France (TT3, 57 km; n = 5). Results: A negative relationship was found between power output (W) at VT (VTWatt) and TT final time (s) in TT1 (r = –0.864; p = 0.026; standard error of estimate (SEE) of 73 s; and 95% confidence limits (95% CL) –0.98; –0.18), TT2 (r = –0.77; p = 0.27; SEE of 139 s; and 95% CL –0.98; 0.35), and TT3 (r = –0.923; p = 0.025; SEE of 94 s; and 95% CL –1.00; –0.22). Conclusions: Actual performance in long TT during the Tour de France (>50 km distance, performed after at least 1–2 weeks of continuous competition), in which some cumulative fatigue inevitably occurs, is related, at least in part, to the power output that elicits the VT. No other routine physiological variable (for example, VO2max or Wpeak) is related to performance in this type of event. PMID:15388555

  1. Pioneer Venus 12.5 km Anomaly Workshop Report, volume 1

    NASA Technical Reports Server (NTRS)

    Seiff, A.; Sromovsky, L.; Borucki, W.; Craig, R.; Juergens, D.; Young, R. E.; Ragent, B.

    1995-01-01

    A workshop was convened at Ames Research Center on September 28 and 29, 1993, to address the unexplained electrical anomalies experienced in December 1978 by the four Pioneer Venus probes below a Venus altitude of 12.5 km. These anomalies caused the loss of valuable data in the deep atmosphere, and, if their cause were to remain unexplained, could reoccur on future Venus missions. The workshop participants reviewed the evidence and studied all identified mechanisms that could consistently account for all observed anomalies. Both hardware problems and atmospheric interactions were considered. Based on a workshop recommendation, subsequent testing identified the cause as being an insulation failure of the external harness. All anomalous events are now explained.

  2. Bicycle weight and commuting time: randomised trial

    PubMed Central

    2010-01-01

    Objective To determine whether the author’s 20.9 lb (9.5 kg) carbon frame bicycle reduced commuting time compared with his 29.75 lb (13.5 kg) steel frame bicycle. Design Randomised trial. Setting Sheffield and Chesterfield, United Kingdom, between mid-January 2010 and mid-July 2010. Participants One consultant in anaesthesia and intensive care. Main outcome measure Total time to complete the 27 mile (43.5 kilometre) journey from Sheffield to Chesterfield Royal Hospital and back. Results The total distance travelled on the steel frame bicycle during the study period was 809 miles (1302 km) and on the carbon frame bicycle was 711 miles (1144 km). The difference in the mean journey time between the steel and carbon bicycles was 00:00:32 (hr:min:sec; 95% CI –00:03:34 to 00:02:30; P=0.72). Conclusions A lighter bicycle did not lead to a detectable difference in commuting time. Cyclists may find it more cost effective to reduce their own weight rather than to purchase a lighter bicycle. PMID:21148220

  3. Geothermal research on the 2.5 km deep COSC-1 drillhole, Central Sweden

    NASA Astrophysics Data System (ADS)

    Pascal, Christophe; Beltrami, Hugo; Daly, Stephen; Juhlin, Christopher; Kukkonen, Ilmo; Long, Mike; Rath, Volker; Renner, Joerg; Schwarz, Gerhard; Sundberg, Jan

    2015-04-01

    The scientific drilling project "Collisional Orogeny in the Scandinavian Caledonides" (COSC), supported by ICDP and the Swedish Research Council, involves the drilling of two boreholes through carefully selected sections of the Paleozoic Caledonian orogen in Central Sweden. COSC-1, the first of the two planned boreholes, was drilled and fully cored down to 2.5 km depth during spring and summer 2014 near the town of Åre. The COSC working group is organised around six thematic teams including us, the geothermal team. The major objectives of the COSC geothermal team are: a) to contribute to basic knowledge about the thermal regime of Palaeozoic orogenic belts, ancient shield areas and high heat-producing plutons; b) to refine knowledge on climate change at high latitudes (i.e. Scandinavia), including historical global changes, recent palaeoclimate development (since last ice age) and expected future trends; c) to determine the vertical variation of the geothermal gradient, heat flow and thermal properties down to 2.5 km, and to determine the required corrections for shallow (< 1 km) heat flow data; d) to explore the geothermal potential of the Åre-Järpen area; e) to explore to what degree the conductive heat transfer is affected by groundwater flow in the uppermost crust and f) to evaluate the heat generation input and impact from the basement and the alum shales. To reach these targets the following tasks were carried out or are planned: 1) heat flow predictions from shallow boreholes; 2) geophysical logging; 3) analyses of logs and well tests; (3) determination of rock thermal properties on core samples; 4) determination of heat generation rates from radiometric and geochemical studies; 5) fracture characterisation for permeability and convective heat flow estimations; 6) analysis of convective signals; 7) analysis of paleoclimatic signals; 8) heat flow modelling and evaluation of geothermal potential and 9) Fennoscandia heat flow map compilation. The purpose of

  4. Physiological determinants of the cycling time trial.

    PubMed

    Støren, Øyvind; Ulevåg, Kåre; Larsen, Morten H; Støa, Eva M; Helgerud, Jan

    2013-09-01

    The purpose of this study was to examine the physiological determinants of endurance cycling time trial (TT) performance in a heterogeneous group of competitive male road cyclists. About 15 male cyclists who had all competed in cycling the preceding season were tested for the anthropometric variables height, body weight, leg length, ankle circumference, and body fat percentage. They were also tested for maximal oxygen consumption (VO2max), lactate threshold (LT), metabolic cost of cycling (CC), peak power output and average power output during a 30-second Wingate test, 1 repetition maximum and peak power in half squats, and a TT test on an ergometer. Heart rate and cadence (rounds per minute, RPM) were continuously measured during all cycle tests. Pearson Bivariate correlation tests and single linear regression tests were performed to obtain correlation coefficients (r), effect size (F), standard error of estimate (SEE), and 95% confidence interval. The single variable that correlated best with TT performance was power output at LT (r = 0.86, p < 0.01). Standard error of estimate was 7.5%. Lactate threshold expressed in %VO2max did not correlate significantly with TT performance. An equation representing both aerobic and anaerobic endurance capacity TT(w) = 0.95 ([VO2max/CC] TT%VO2max) + 0.05 (Wingate average) correlated strongly with TT laboratory performance (r = 0.93, p < 0.01, SEE = 5.7%). None of the strength, power, or anthropometric variables correlated significantly with TT laboratory performance.

  5. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2016-02-01

    This study presents a high-resolution (˜ 5.5 km) estimate of surface mass balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a firn densification model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in situ SMB observations and discharge rates from six glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes, complicating a full model evaluation. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 in the western AP (WAP) and below 500 mm we yr-1 in the eastern AP (EAP), not resolved by coarser data sets such as ERA-Interim. The average AP ice-sheet-integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the modelled AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr-2).

  6. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2015-09-01

    This study presents a high-resolution (~ 5.5 km) estimate of Surface Mass Balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a Firn Densification Model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in-situ SMB observations and discharge rates from 6 glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 over the western AP (WAP) and below 500 mm we yr-1 on the eastern AP (EAP), not resolved by coarser data-sets such as ERA-Interim. The other SMB components are one order of magnitude smaller, with drifting snow sublimation the largest ablation term removing up to 100 mm we yr-1 of mass. Snowmelt is widespread over the AP, reaching 500 mm we yr-1 towards the northern ice shelves, but the meltwater mostly refreezes. As a result runoff fluxes are low, but still considerable (200 mm we yr-1) over the Larsen (B/C), Wilkins and George VI ice shelves. The average AP ice sheet integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the AP SMB components, except

  7. Effects of power variation on cycle performance during simulated hilly time-trials.

    PubMed

    Wells, Marc S; Marwood, Simon

    2016-11-01

    It has previously been shown that cyclists are unable to maintain a constant power output during cycle time-trials on hilly courses. The purpose of the present study is therefore to quantify these effects of power variation using a mathematical model of cycling performance. A hypothetical cyclist (body mass: 70 kg, bicycle mass: 10 kg) was studied using a mathematical model of cycling, which included the effects of acceleration. Performance was modelled over three hypothetical 40-km courses, comprising repeated 2.5-km sections of uphill and downhill with gradients of 1%, 3%, and 6%, respectively. Amplitude (5-15%) and distance (0.31-20.00 km) of variation were modelled over a range of mean power outputs (200-600 W) and compared to sustaining a constant power. Power variation was typically detrimental to performance; these effects were augmented as the amplitude of variation and severity of gradient increased. Varying power every 1.25 km was most detrimental to performance; at a mean power of 200 W, performance was impaired by 43.90 s (±15% variation, 6% gradient). However at the steepest gradients, the effect of power variation was relatively independent of the distance of variation. In contrast, varying power in parallel with changes in gradient improved performance by 188.89 s (±15% variation, 6% gradient) at 200 W. The present data demonstrate that during hilly time-trials, power variation that does not occur in parallel with changes in gradient is detrimental to performance, especially at steeper gradients. These adverse effects are substantially larger than those previously observed during flat, windless time-trials.

  8. Hybrid fine scale climatology and microphysics of in-cloud icing: From 32 km reanalysis to 5 km mesoscale modeling

    NASA Astrophysics Data System (ADS)

    Lamraoui, Fayçal; Benoit, Robert; Perron, Jean; Fortin, Guy; Masson, Christian

    2015-03-01

    In-cloud icing can impose safety concerns and economic challenges for various industries. Icing climate representations proved beneficial for optimal designs and careful planning. The current study investigates in-cloud icing, its related cloud microphysics and introduces a 15-year time period climatology of icing events. The model was initially driven by reanalysis data from North American Regional Reanalysis and downscaled through a two-level nesting of 10 km and 5 km, using a limited-area version of the Global Environment Multiscale Model of the Canadian Meteorological Center. In addition, a hybrid approach is used to reduce time consuming calculations. The simulation realized exclusively on significant icing days, was combined with non-significant icing days as represented by data from NARR. A proof of concept is presented here for a 1000 km area around Gaspé during January for those 15 years. An increase in the number and intensity of icing events has been identified during the last 15 years. From GEM-LAM simulations and within the atmospheric layer between 10 m and 200 m AGL, supercooled liquid water contents indicated a maximum of 0.4 g m- 3, and 50% of the values are less than 0.05 g m- 3. All values of median volume diameters (MVD) are approximately capped by 70 μm and the typical values are around 15 μm. Supercooled Large Droplets represent approximately 5%. The vertical profile of icing climatology demonstrates a steady duration of icing events until the level of 60 m. The altitudes of 60 m and 100 m indicate substantial icing intensification toward higher elevations. GEM-LAM demonstrated a substantial improvement in the calculation of in-cloud icing, reducing significantly the challenge posed by complex terrains.

  9. Variable versus constant power strategies during cycling time-trials: prediction of time savings using an up-to-date mathematical model.

    PubMed

    Atkinson, G; Peacock, O; Passfield, L

    2007-07-01

    Swain (1997) employed the mathematical model of Di Prampero et al. (1979) to predict that, for cycling time-trials, the optimal pacing strategy is to vary power in parallel with the changes experienced in gradient and wind speed. We used a more up-to-date mathematical model with validated coefficients (Martin et al., 1998) to quantify the time savings that would result from such optimization of pacing strategy. A hypothetical cyclist (mass = 70 kg) and bicycle (mass = 10 kg) were studied under varying hypothetical wind velocities (-10 to 10 m x s(-1)), gradients (-10 to 10%), and pacing strategies. Mean rider power outputs of 164, 289, and 394 W were chosen to mirror baseline performances studied previously. The three race scenarios were: (i) a 10-km time-trial with alternating 1-km sections of 10% and -10% gradient; (ii) a 40-km time-trial with alternating 5-km sections of 4.4 and -4.4 m x s(-1) wind (Swain, 1997); and (iii) the 40-km time-trial delimited by Jeukendrup and Martin (2001). Varying a mean power of 289 W by +/- 10% during Swain's (1997) hilly and windy courses resulted in time savings of 126 and 51 s, respectively. Time savings for most race scenarios were greater than those suggested by Swain (1997). For a mean power of 289 W over the "standard" 40-km time-trial, a time saving of 26 s was observed with a power variability of 10%. The largest time savings were found for the hypothetical riders with the lowest mean power output who could vary power to the greatest extent. Our findings confirm that time savings are possible in cycling time-trials if the rider varies power in parallel with hill gradient and wind direction. With a more recent mathematical model, we found slightly greater time savings than those reported by Swain (1997). These time savings compared favourably with the predicted benefits of interventions such as altitude training or ingestion of carbohydrate-electrolyte drinks. Nevertheless, the extent to which such power output variations

  10. A crater 1.5 km across in the Venera-13 panoramic image taken on the surface of the planet

    NASA Astrophysics Data System (ADS)

    Ksanfomality, L. V.

    2014-11-01

    The reprocessing of the archive data of the television experiment performed by the Venera-13 spacecraft in 1982 on the surface of the planet allowed an image of the nearby crater 1.5 km across to be obtained in detail. Its structural features apparently indicate its volcanic origin. All of the earlier acquired analogous images of such formations were composed only from the orbital radar data and correspond to the sizes of tens of kilometers.

  11. Earthquake source scaling relationships from -1 to 5 ML using seismograms recorded at 2.5-km depth

    NASA Astrophysics Data System (ADS)

    Abercrombie, Rachel E.

    1995-12-01

    The scaling relationships of earthquake sources less than about magnitude 3 have been the subject of considerable controversy over the last two decades. Studies of such events have shown a tendency for the constant stress drop, self similarity of larger earthquakes to breakdown at small magnitudes, and an apparent minimum source dimension of about 100 m has been observed. Other studies showed that this apparent breakdown in scaling could be an artifact of severe near-surface attenuation, limiting the spatial resolution of surface data. In this study, source parameters are determined for over 100 nearby, tectonic earthquakes, from recordings at a depth of 2.5 km (in granite) in the Cajon Pass scientific drill hole, southern California. Comparison of the seismograms recorded at this depth with those at the wellhead clearly demonstrates the effect of the severe attenuation in the upper kilometers of the Earth's crust. Source parameters are calculated by spectral modeling of three-component P and S waves, assuming four source models based on the Brune ω-2 (n = 2) model. In model l, n = 2 is fixed, and Q of P and S waves is determined to be 912 (581-1433) and 1078 (879-1323), respectively (the numbers in parentheses are ±1 standard deviation). In model 2, QP = QS = 1000 is assumed and n is allowed to vary. The ω-2 model is a good average for the data set, but there is some real scatter supported by the data. In model 3, QP = QS = 1000 is also assumed and ω-2 is constrained, and in model 4, attenuation is ignored and n is allowed to vary. Source dimensions of less than 10m are observed for all four models, 10 times smaller than the proposed "minimum". No breakdown in constant stress drop scaling is seen in the downhole data (approximately ML-1 to 5.5, M0 = 109 - 1016 Nm). The ratio between radiated seismic energy (estimated by integrating the velocity squared spectra with adequate signal bandwidth) and seismic moment appears to decrease gradually with decreasing

  12. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed Central

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

  13. Application of scalar timing theory to individual trials.

    PubMed

    Church, R M; Meck, W H; Gibbon, J

    1994-04-01

    Our purpose was to infer the characteristics of the internal clock, temporal memory, and decision processes involved in temporal generalization behavior on the basis of the analysis of individual trials. Three groups of 10 rats each were trained on a peak procedure with reinforcement at 15, 30, or 60 s, with several nonfood trial durations. On nonfood trials, the mean response rate gradually increased to a maximum near the time that reinforcement sometimes occurred and then gradually decreased. Individual trials were characterized by a period of high response rate, preceded and followed by a low response rate. The covariance pattern among measures of the temporal characteristics of the high response rate (start, stop, middle, and spread) supported a parallel, scalar timing model in which animals used on each trial a single sample from memory of the time of reinforcement and separate response thresholds to decide when to start and stop responding. An alternative model, the quasi-serial model (J. Gibbon & R. M. Church, 1992), was not consistent with the obtained relationships between covariances or with the scalar property seen across different nonfood signal durations.

  14. Time Trials--An AP Physics Challenge Lab

    ERIC Educational Resources Information Center

    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…

  15. Effect of Overhydration on Time-Trial Swim Performance.

    ERIC Educational Resources Information Center

    Maresh, Carl M.; Bergeron, Michael E.; Kenefick, Robert W.; Castellani, John W.; Hoffman, Jay R.; Armstrong, Lawrence E.

    2001-01-01

    Examined whether moderate overhydration would enhance the performance of otherwise euhydrated collegiate swimmers during two 183-meter time-trial swims held 3 days apart. Participants swam in alternate, randomized euhydrated, and overhydrated states. Results indicated that euhydration before an intense, short-duration swim was adequate for peak…

  16. Improving time-lapse seismic repeatability: CO2CRC Otway site permanent geophone array field trials

    NASA Astrophysics Data System (ADS)

    Pevzner, Roman; Dupuis, Christian; Shulakova, Valeriya; Urosevic, Milovan; Lumley, David

    2013-04-01

    The proposed Stage 2C of the CO2CRC Otway project involves injection of a small amount (around 15,000 tonnes) of CO2/CH4 gas mixture into saline acquifer (Paaratte formation) at the depth of ~1.5 km. The seismic time-lapse signal will depend largely on the formation properties and the injection scenario, but is likely to be relatively weak. In order to improve time-lapse seismic monitoring capabilities by decreasing the noise level, a buried receiver arrays can be used. A small-scale trial of such an array was conducted at Otway site in June 2012. A set of 25 geophones was installed in 3 m deep boreholes in parallel to the same number of surface geophones. In addition, four geophones were placed into boreholes of 1 to 12 m depth. In order to assess the gain in the signal-to-noise ratio and repeatability, both active and passive seismic surveys were carried out. The surveys were conducted in relatively poor weather conditions, with rain, strong wind and thunderstorms increasing the noise level. We found that noise level for buried geophones is on average 20 dB lower compared to the surface ones. Furthermore, the combination of active and passive experiments has allowed us to perform a detailed classification of various noise sources. Acknowledgement The authors acknowledge the funding provided by the Australian government through its CRC program to support this CO2CRC research project. We also acknowledge the CO2CRC's corporate sponsors and the financial assistance provided through Australian National Low Emissions Coal Research and Development (ANLEC R&D). ANLEC R&D is supported by Australian Coal Association Low Emissions Technology Limited and the Australian Government through the Clean Energy Initiative.

  17. The analysis and modeling of the ARDEC 2.5 km/s 20-mm plasma railgun shot

    NASA Astrophysics Data System (ADS)

    Sink, D. A.; Chang, D. I.; Davis, A.; Colombo, G.; Hildenbrand, D. J.

    1993-01-01

    The 20-mm round-bore plasma railgun was successfully fired at the ARDEC electric gun facility. The 4-m gun with copper rails and alumina composite insulators was operated using a light-gas gun injector to start the projectile, already located in the gun, moving prior to the introduction of current. Current from the EMACK homopolar generator (HPG) was commutated into the gun by an explosively-actuated opening switch. The muzzle velocity was recorded by breakwires and flash X-rays at 2.5 km/s. B-dot sensors, rail current Rogowski coils, and breech and muzzle voltage measurements provided data on the in-bore dynamics of the armature. Post-shot analysis using the ARMRAIL (ARMature Physics and RAILgun Performance Model) code successfully provided calculations reproducing all the main features of the data. Models account for the observed secondary arcs present throughout the shot and the basis for the code and physics modeling is given.

  18. Pseudoephedrine ingestion and cycling time-trial performance.

    PubMed

    Pritchard-Peschek, Kellie R; Jenkins, David G; Osborne, Mark A; Slater, Gary J

    2010-04-01

    The aim of the current study was to investigate the effect of 180 mg of pseudoephedrine (PSE) on cycling time-trial (TT) performance. Six well-trained male cyclists and triathletes (age 33 +/- 2 yr, mass 81 +/- 8 kg, height 182.0 +/- 6.7 cm, VO2max 56.8 +/- 6.8 ml x kg(-1) x min(-1); M +/- SD) underwent 2 performance trials in which they completed a 25-min variable-intensity (50-90% maximal aerobic power) warm-up, followed by a cycling TT in which they completed a fixed amount of work (7 kJ/kg body mass) in the shortest possible time. Sixty minutes before the start of exercise, they orally ingested 180 mg of PSE or a cornstarch placebo (PLA) in a randomized, crossover, double-blind manner. Venous blood was sampled immediately pre- and postexercise for the analysis of pH plus lactate, glucose, and norepinephrine (NE). PSE improved cycling TT performance by 5.1% (95% CI 0-10%) compared with PLA (28:58.9 +/- 4:26.5 and 30:31.7 +/- 4:36.7 min, respectively). There was a significant Treatment x Time interaction (p = .04) for NE, with NE increasing during the PSE trial only. Similarly, blood glucose also showed a trend (p = .06) for increased levels postexercise in the PSE trial. The ingestion of 180 mg of PSE 60 min before the onset of high-intensity exercise improved cycling TT performance in well-trained athletes. It is possible that changes in metabolism or an increase in central nervous system stimulation is responsible for the observed ergogenic effect of PSE.

  19. The effects of caffeinated "energy shots" on time trial performance.

    PubMed

    Schubert, Matthew Mark; Astorino, Todd Anthony; Azevedo, John Leal

    2013-06-01

    An emerging trend in sports nutrition is the consumption of energy drinks and "energy shots". Energy shots may prove to be a viable pre-competition supplement for runners. Six male runners (mean ± SD age and VO2max: 22.5 ± 1.8 years and 69.1 ± 5.7 mL·kg-1·min-1) completed three trials [placebo (PLA; 0 mg caffeine), Guayakí Yerba Maté Organic Energy Shot™ (YM; 140 mg caffeine), or Red Bull Energy Shot™ (RB; 80 mg caffeine)]. Treatments were ingested following a randomized, placebo-controlled crossover design. Participants ran a five kilometer time trial on a treadmill. No differences (p > 0.05) in performance were detected with RB (17.55 ± 1.01 min) or YM ingestion (17.86 ± 1.59 min) compared to placebo (17.44 ± 1.25 min). Overall, energy shot ingestion did not improve time-trial running performance in trained runners. PMID:23743969

  20. Sodium phosphate supplementation and time trial performance in female cyclists.

    PubMed

    Buck, Christopher L; Dawson, Brian; Guelfi, Kym J; McNaughton, Lars; Wallman, Karen E

    2014-09-01

    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. Key PointsNo significant benefit of a 25, 50 or 75 mg·kg(-1) of FFM dose of sodium phosphate was found on 500 kJ (119.5 Kcal) TT cycle performance in female cyclists.Females of differing fitness levels responded similarly to sodium phosphate supplementation.Due to the possibility of individual responders to either the 50 or 75 mg·kg(-1) of FFM loading protocols, competitive cyclists should trial these doses prior to competition.

  1. 3D seismic imaging around the 2.5 km deep COSC-1 scientific borehole, central Sweden

    NASA Astrophysics Data System (ADS)

    Hedin, Peter; Juhlin, Christopher; Buske, Stefan

    2015-04-01

    Following the successful completion of the COSC-1 drilling campaign, a number of geophysical investigations have been performed in and around the 2.5 km deep borehole. Three different seismic experiments were conducted simultaneously in the fall of 2014 to take advantage of the same source points; 1) a Vertical Seismic Profile (VSP) in the borehole, 2) three 2D seismic profiles across the borehole, and 3) a limited 3D seismic survey (presented here). The latter is the first 3D seismic survey on land in Scandinavia to target the Caledonian Nappes and will allow mapping a small part of the Seve Nappe Complex (SNC) in 3D. Furthermore, it will allow extrapolation of results from downhole logging, core analysis and other seismic surveys to structures surrounding the borehole. A total number of 429 receivers (10 Hz single component geophones) were planted with 20 m separation along 7 lines spaced 200 m apart. The total area with receivers covered approximately 1.5 km2 and was centered on the drill site. A combination of a mechanical source (a rock breaking hydraulic hammer, near offsets) and explosive charges (0.5 kg fired at 3.5 - 5 m depth, far offsets) were used. The source points were activated along roads radiating outwards from the COSC-1 drill site in a star pattern. The nominal shot spacing was 20 m (vibrating source) or 80 m (explosives) and maximum horizontal offset was about 5.75 km. The high-grade metamorphic SNC is well known from previous 2D seismic studies to be a highly reflective unit. However, due to the complex 3D geometry and lithological variation within the unit, it has not been clearly imaged. The new 3D data provide a means to image these structures in more detail and to follow the lithological and structural interfaces observed in the core into the surrounding unit. Preliminary results from the 3D processing and correlation with borehole data will be presented.

  2. Future climate changes in Greenland during the 21st century at a 5km resolution using HIRHAM5

    NASA Astrophysics Data System (ADS)

    Boberg, Fredrik

    2016-04-01

    DMI has estimated the expected climate change in Greenland, based on the latest Danish and international scenario calculations, focusing on climate change within this century and the emission scenarios used by IPCC. A large number of climate indices designed for Greenlandish conditions have been calculated using output from the HIRHAM5 regional climate model run at a 5km horizontal resolution. Climate simulations and understanding of associated uncertainties are constantly being improved. Here we utilize a statistical method on an ensemble of CMIP5 GCMs to assess uncertainties of projected climate change results based on the DMI high resolution regional model. For specific planning, assessment and risk analysis of climate adaptation, it is important to consider the full range of estimates as indicated by the uncertainty interval, instead of simply considering the best estimate. Climate variability and change are expected to increase towards 2100 in terms of higher temperatures, more winter precipitation, longer growing seasons, reduction of permafrost, more frequent and more extreme weather events and a continuing loss of sea ice.

  3. The accuracy of simulated indoor time trials utilizing a CompuTrainer and GPS data.

    PubMed

    Peveler, Willard W

    2013-10-01

    The CompuTrainer is commonly used to measure cycling time trial performance in a laboratory setting. Previous research has demonstrated that the CompuTrainer tends toward underestimating power at higher workloads but provides reliable measures. The extent to which the CompuTrainer is capable of simulating outdoor time trials in a laboratory setting has yet to be examined. The purpose of this study was to examine the validity of replicating an outdoor time trial course indoors by comparing completion times between the actual time trial course and the replicated outdoor time trial course on the CompuTrainer. A global positioning system was used to collect data points along a local outdoor time trial course. Data were then downloaded and converted into a time trial course for the CompuTrainer. Eleven recreational to highly trained cyclists participated in this study. To participate in this study, subjects had to have completed a minimum of 2 of the local Cleves time trial races. Subjects completed 2 simulated indoor time trials on the CompuTrainer. Mean finishing times for the mean indoor performance trial (34.58 ± 8.63 minutes) were significantly slower in relation to the mean outdoor performance time (26.24 ± 3.23 minutes). Cyclists' finish times increased (performance decreased) by 24% on the indoor time trials in relation to the mean outdoor times. There were no significant differences between CompuTrainer trial 1 (34.77 ± 8.54 minutes) and CompuTrainer trial 1 (34.37 ± 8.76 minutes). Because of the significant differences in times between the indoor and outdoor time trials, meaningful comparisons of performance times cannot be made between the two. However, there were no significant differences found between the 2 CompuTrainer trials, and therefore the CompuTrainer can still be recommended for laboratory testing between trials.

  4. Collisional Orogeny in the Scandinavian Caledonides (COSC): Scientific objectives for the planned 2.5 km deep COSC-2 borehole

    NASA Astrophysics Data System (ADS)

    Juhlin, Christopher; Anderson, Mark; Dopson, Mark; Lorenz, Henning; Pascal, Christophe; Piazolo, Sandra; Roberts, Nick; Rosberg, Jan-Erik; Tsang, Chin-Fu

    2016-04-01

    The Collisional Orogeny in the Scandinavian Caledonides (COSC) scientific drilling project employs two fully cored boreholes for investigating mountain building processes at mid-crustal levels in a deeply eroded Paleozoic collisional orogen of Alpine-Himalayan size. The two COSC boreholes will provide a unique c. 5 km deep composite section from a hot allochthon through the underlying 'colder' nappes, the main décollement and into the basement of the collisional underriding plate. COSC's unprecedented wealth of geophysical field and borehole data combined with the petrology, geochronology and rock physics information obtained from the drill cores will develop into an integrated model for a major collisional mountain belt. This can be utilized as an analogue to better understand similar modern tectonic settings (Himalaya, Izu-Bonin-Mariana, amongst others) and, thus, advance our understanding of such complex systems and how they affect the (human) environment. COSC investigations and drilling activities are focused in the Åre-Mörsil area (Sweden) of central Scandinavia. The first drill hole, COSC-1, was completed in late August 2014 with near 100% core recovery down to 2.5 km. It targeted the high-grade metamorphic Seve Nappe Complex (SNC) and its contact with the underlying allochthon, investigating how this metasedimentary unit, that was initially deeply subducted during orogeny, was exhumed and then, still hot, emplaced as an allochthon onto the foreland of the underriding plate. COSC-2 will investigate the main Caledonian décollement, which is the major detachment that separates the Caledonian allochthons from the autochthonous basement of the Fennoscandian Shield, and the character of the deformation in the basement. Combined seismic, magnetotelluric (MT) and magnetic data provide control on the basement structure and the depth to the main décollement, believed to be hosted in the carbon-rich highly conductive Alum Shale. Key targets are to understand the

  5. Timing in free-operant and discrete-trial avoidance.

    PubMed

    Hineline, P N; Herrnstein, R J

    1970-03-01

    A procedure ("discrete-trial" avoidance) was devised to differentiate between the two main theories of responding in Sidman's "free-operant" avoidance procedure. One theory, a version of two-factor theory, holds that responding is reinforced by the removal of a conditioned aversive stimulus. The conditioned aversive stimulus is held to be temporal, which accounts for the spaced responding, or timing, that Sidman's procedure produces. The other theory holds that the reinforcement for both responding and timing is shock-frequency reduction. The new procedure eliminated this reinforcement for timing, but retained the conditions for the formation of conditioned aversive temporal stimuli. According to one theory, the new procedure should have sustained timing as well as Sidman's, while according to the other, it should have sustained no timing. The results confirmed neither theory. Timing was found with both procedures, but unequally in degree and kind. Large variations in the precision of timing did not appear to be correlated with successful avoidance for either procedure.

  6. Effect of astaxanthin on cycling time trial performance.

    PubMed

    Earnest, C P; Lupo, M; White, K M; Church, T S

    2011-11-01

    We examined the effect of Astaxanthin (AST) on substrate metabolism and cycling time trial (TT) performance by randomly assigning 21 competitive cyclists to 28 d of encapsulated AST (4 mg/d) or placebo (PLA) supplementation. Testing included a VO2max test and on a separate day a 2 h constant intensity pre-exhaustion ride, after a 10 h fast, at 5% below VO2max stimulated onset of 4 mmol/L lactic acid followed 5 min later by a 20 km TT. Analysis included ANOVA and post-hoc testing. Data are Mean (SD) and (95% CI) when expressed as change (pre vs. post). Fourteen participants successfully completed the trial. Overall, we observed significant improvements in 20 km TT performance in the AST group (n=7; -121 s; 95% CI, -185, -53), but not the PLA (n=7; -19 s; 95% CI, -84, 45). The AST group was significantly different vs. PLA (P<0.05). The AST group significantly increased power output (20 W; 95% CI, 1, 38), while the PLA group did not (1.6 W; 95% CI, -17, 20). The mechanism of action for these improvements remains unclear, as we observed no treatment effects for carbohydrate and fat oxidation, or blood indices indicative of fuel mobilization. While AST significantly improved TT performance the mechanism of action explaining this effect remains obscure.

  7. Seismic imaging in the eastern Scandinavian Caledonides: siting the 2.5 km deep COSC-2 borehole, central Sweden

    NASA Astrophysics Data System (ADS)

    Juhlin, Christopher; Hedin, Peter; Gee, David G.; Lorenz, Henning; Kalscheuer, Thomas; Yan, Ping

    2016-05-01

    The Collisional Orogeny in the Scandinavian Caledonides (COSC) project, a contribution to the International Continental Scientific Drilling Program (ICDP), aims to provide a deeper understanding of mountain belt dynamics. Scientific investigations include a range of topics, from subduction-related tectonics to the present-day hydrological cycle. COSC investigations and drilling activities are focused in central Scandinavia, where rocks from the middle to lower crust of the orogen are exposed near the Swedish-Norwegian border. Here, rock units of particular interest occur in the Seve Nappe Complex (SNC) of the so-called Middle Allochthon and include granulite facies migmatites (locally with evidence of ultra-high pressures) and amphibolite facies gneisses and mafic rocks. This complex overlies greenschist facies metasedimentary rocks of the dolerite-intruded Sarv Nappes and underlying, lower grade Jamtlandian Nappes (Lower Allochthon). Reflection seismic profiles have been an important component in the activities to image the subsurface structure in the area. Subhorizontal reflections in the upper 1-2 km are underlain and interlayered with strong west- to northwest-dipping reflections, suggesting significant east-vergent thrusting. Two 2.5 km deep fully cored boreholes are a major component of the project, which will improve our understanding of the subsurface structure and tectonic history of the area. Borehole COSC-1 (IGSN: http://hdl.handle.net/10273/ICDP5054EEW1001), drilled in the summer of 2014, targeted the subduction-related Seve Nappe Complex and the contact with the underlying allochthon. The COSC-2 borehole will be located further east and will investigate the lower grade, mainly Cambro-Silurian rocks of the Lower Allochthon, the Jamtlandian decollement, and penetrate into the crystalline basement rocks to identify the source of some of the northwest-dipping reflections. A series of high-resolution seismic profiles have been acquired along a composite ca

  8. Continuous measurements of water surface height and width along a 6.5km river reach for discharge algorithm development

    NASA Astrophysics Data System (ADS)

    Tuozzolo, S.; Durand, M. T.; Pavelsky, T.; Pentecost, J.

    2015-12-01

    The upcoming Surface Water and Ocean Topography (SWOT) satellite will provide measurements of river width and water surface elevation and slope along continuous swaths of world rivers. Understanding water surface slope and width dynamics in river reaches is important for both developing and validating discharge algorithms to be used on future SWOT data. We collected water surface elevation and river width data along a 6.5km stretch of the Olentangy River in Columbus, Ohio from October to December 2014. Continuous measurements of water surface height were supplemented with periodical river width measurements at twenty sites along the study reach. The water surface slope of the entire reach ranged from during 41.58 cm/km at baseflow to 45.31 cm/km after a storm event. The study reach was also broken into sub-reaches roughly 1km in length to study smaller scale slope dynamics. The furthest upstream sub-reaches are characterized by free-flowing riffle-pool sequences, while the furthest downstream sub-reaches were directly affected by two low-head dams. In the sub-reaches immediately upstream of each dam, baseflow slope is as low as 2 cm/km, while the furthest upstream free-flowing sub-reach has a baseflow slope of 100 cm/km. During high flow events the backwater effect of the dams was observed to propagate upstream: sub-reaches impounded by the dams had increased water surface slopes, while free flowing sub-reaches had decreased water surface slopes. During the largest observed flow event, a stage change of 0.40 m affected sub-reach slopes by as much as 30 cm/km. Further analysis will examine height-width relationships within the study reach and relate cross-sectional flow area to river stage. These relationships can be used in conjunction with slope data to estimate discharge using a modified Manning's equation, and are a core component of discharge algorithms being developed for the SWOT mission.

  9. A Time-Trend Economic Analysis of Cancer Drug Trials

    PubMed Central

    Browman, George P.; Hoch, Jeffrey S.; Kovacic, Laurel; Peacock, Stuart J.

    2015-01-01

    Background. Scientific advances have led to the discovery of novel treatments with high prices. The cost to publicly fund high-cost drugs may threaten the sustainability of drug budgets in different health care systems. In oncology, there are concerns that health-benefit gains are diminishing over time and that the economic evidence to support funding decisions is too limited. Methods. To assess the additional costs and benefits gained from oncology drugs over time, we used treatment protocols and efficacy results from U.S. Food and Drug Administration records to calculate cost-effectiveness ratios for drugs approved to treat first- and second-line metastatic or advanced breast, colorectal, and non-small cell lung cancer during the years 1994–2013. We assessed reimbursement recommendations reached by health technology assessment agencies in the U.K., Australia, and Canada. Results. Cost-effectiveness ratios were calculated for 50 drugs approved by the U.S. regulator. The more recent approvals were often based on surrogate efficacy outcomes and had extremely high costs, often triple the costs of drugs approved in previous years. Over time, the effectiveness gains have increased for some cancer indications; however, for other indications (non-small cell lung and second-line colorectal cancer), the magnitude of gains in effectiveness decreased. Reimbursement recommendations for drugs with the highest cost-effectiveness ratios were the most inconsistent. Conclusion. Evaluation of the clinical benefits that oncology drugs offer as a function of their cost has become highly complex, and for some clinical indications, health benefits are diminishing over time. There is an urgent need for better economic evidence from oncology drug trials and systematic processes to inform funding decisions. Implications for Practice: High-cost oncology drugs may threaten the ability of health care systems to provide access to promising new drugs for patients. In order to make better

  10. Steps and Time to Process Clinical Trials at the Cancer Therapy Evaluation Program

    PubMed Central

    Dilts, David M.; Sandler, Alan B.; Cheng, Steven K.; Crites, Joshua S.; Ferranti, Lori B.; Wu, Amy Y.; Finnigan, Shanda; Friedman, Steven; Mooney, Margaret; Abrams, Jeffrey

    2009-01-01

    Purpose To examine the processes and document the calendar time required for the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) and Central Institutional Review Board (CIRB) to evaluate and approve phase III clinical trials. Methods Process steps were documented by (1) interviewing CTEP and CIRB staff regarding the steps required to activate a trial from initial concept submission to trial activation by a cooperative group, (2) reviewing standard operating procedures, and (3) inspecting trial records and documents for selected trials to identify any additional steps. Calendar time was collected from initial concept submission to activation using retrospective data from the CTEP Protocol and Information Office. Results At least 296 distinct processes are required for phase III trial activation: at least 239 working steps, 52 major decision points, 20 processing loops, and 11 stopping points. Of the 195 trials activated during the January 1, 2000, to December 31, 2007, study period, a sample of 167 (85.6%) was used for gathering timing data. Median calendar days from initial formal concept submission to CTEP to trial activation by a cooperative group was 602 days (interquartile range, 454 to 861 days). This time has not significantly changed over the past 8 years. There is a high variation in the time required to activate a clinical trial. Conclusion Because of their complexity, the overall development time for phase III clinical trials is lengthy, process laden, and highly variable. To streamline the process, a solution must be sought that includes all parties involved in developing trials. PMID:19255315

  11. Impact Craters of Venus with D Greater Than 5 km Classified Based on Degree of Preservation of the Associated Radar-Dark Deposits

    NASA Technical Reports Server (NTRS)

    Basilevsky, A. T.; Head, J. W.; Setyaeva, I. V.

    2003-01-01

    This is a further continuation of work, which studied craters greater than or equal to 30 km in diameter. That work subdivided craters based on character of the associated radar dark deposits. It was suggested and then confirmed that the most pristine deposits of that sort are radar-dark parabolas. Non-parabolic radar-dark halos represent the next stage of the deposit evolution and then with time they disappear. So presence and character of crater-associated dark deposit can be used for estimates of the crater age and then for dating other features. Previous work classified craters into: 1) craters with dark parabola (DP), 2) with clear dark halo (CH), 3) with faint halo (FH) and 4) with no dark halo (NH). It was found that abundances of craters superposed on regional plains (whose mean age is close to the planet mean surface age T) and belonging to DP, CH, FH and NH classes were correspondingly 15, 30, 30 and 25%. From that it was concluded that DP craters are not older than 0.1-0.15T; CH craters formed during the time interval from approx. 0.5T until 0.1-0.15T ago, and the FH and NH craters formed prior to approx. 0.5T ago. It was shown that the DP, CH, FH and NH percentages show only slight apparent dependence on the crater geographic latitudes and no noticeable dependence on the crater size. The present study analyzes a much larger population (all D greater than or equal to 5 km craters) to investigate better the latitude effect and to study if within this larger crater population the size effect exists.

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

    PubMed

    Adleman, Nancy E; Chen, Gang; Reynolds, Richard C; Frackman, Anna; Razdan, Varun; Weissman, Daniel H; Pine, Daniel S; Leibenluft, Ellen

    2016-06-01

    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.

  13. Real-Time Enrollment Dashboard For Multisite Clinical Trials

    PubMed Central

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

    2015-01-01

    Objective 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. Materials and Methods 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. Results 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. 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 a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system. PMID:26878068

  14. Measurements of laser phase fluctuations induced by atmospheric turbulence over 2 km and 17.5 km distances.

    PubMed

    Ridley, Kevin D

    2011-09-10

    A laser heterodyne system was used to measure the phase fluctuations imposed on a 1.5 μm wavelength laser beam when double-passed over long atmospheric paths. Two distances were used: 2 and 17.5 km. Results are given for intensity scintillation, phase fluctuation time series and spectra, and phase structure function. The results are found to agree well with theory: the spectrum of phase fluctuations follows the 8/3 power law predicted for Kolmogorov turbulence over 3 orders of magnitude in frequency. The methods reported here could be used to investigate large-scale temperature variations in the atmosphere. PMID:21946989

  15. Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots

    PubMed Central

    Tošić, Tamara; Sellers, Kristin K.; Fröhlich, Flavio; Fedotenkova, Mariia; beim Graben, Peter; Hutt, Axel

    2016-01-01

    For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain. PMID:26834580

  16. DEEP BIOSPHERE. Exploring deep microbial life in coal-bearing sediment down to ~2.5 km below the ocean floor.

    PubMed

    Inagaki, F; Hinrichs, K-U; Kubo, Y; Bowles, M W; Heuer, V B; Hong, W-L; Hoshino, T; Ijiri, A; Imachi, H; Ito, M; Kaneko, M; Lever, M A; Lin, Y-S; Methé, B A; Morita, S; Morono, Y; Tanikawa, W; Bihan, M; Bowden, S A; Elvert, M; Glombitza, C; Gross, D; Harrington, G J; Hori, T; Li, K; Limmer, D; Liu, C-H; Murayama, M; Ohkouchi, N; Ono, S; Park, Y-S; Phillips, S C; Prieto-Mollar, X; Purkey, M; Riedinger, N; Sanada, Y; Sauvage, J; Snyder, G; Susilawati, R; Takano, Y; Tasumi, E; Terada, T; Tomaru, H; Trembath-Reichert, E; Wang, D T; Yamada, Y

    2015-07-24

    Microbial life inhabits deeply buried marine sediments, but the extent of this vast ecosystem remains poorly constrained. Here we provide evidence for the existence of microbial communities in ~40° to 60°C sediment associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas compositions. Concentrations of indigenous microbial cells below 1.5 km ranged from <10 to ~10(4) cells cm(-3). Peak concentrations occurred in lignite layers, where communities differed markedly from shallower subseafloor communities and instead resembled organotrophic communities in forest soils. This suggests that terrigenous sediments retain indigenous community members tens of millions of years after burial in the seabed.

  17. Long Term Borehole Monitoring System For NanTroSEIZE 3.5 km Riser Hole: Requirements And Specifications

    NASA Astrophysics Data System (ADS)

    Kuramoto, S.; Kyo, M.; Ito, H.; Namba, Y.; Kato, K.; Higuchi, K.; Kinoshita, M.; Araki, E.; Suyehiro, K.

    2007-12-01

    Most of the large earthquakes (magnitude greater than 8.0) observed in Japan fall into the subduction plate- boundary category. Based on the results of previous Nankai Trough research efforts, further research opportunities have been proposed under the umbrella of the IODP scientific drilling proposal 603 (NanTroSEIZE: Nankai Trough Seismogenic Zone Experiment) ranked as the top level proposal in IODP. IODP proposal 603 not only proposes drilling, coring and geological analysis, and geophysical logging, but also mandates that a long- term borehole monitoring system be installed into two deep riser holes at about 3,500 m and about 6,000 m below sea floor (mbsf), where we expect to encounter the mega-splay and the locked region of mega thrust fault, respectively. The first riser target (NT2-03 site) is expected to drill through five potential splay faults above 3,500 mbsf. We plan to install sensors to monitor strain, tilt and optionally pore pressure for crustal deformation at and between splay faults, to monitor seismometer array for micro and slow earthquakes detection and for seismic microstructures, and to monitor pore pressure and temperature for hydrologic state change at the fault during interseismic period. The major technical features to develop the deep ocean borehole observatory for NT2-03A are mainly as follows; 1) high temperature (125°E#8249;C), 2) long life (5 years), 3) deployment (15,000 psi wellhead system, deep well, retrieval, perforation, packer, mechanical shock), 4) coupling to formation (cement, clamp), 5) multi level monitoring (against 5 spray faults), 6) multi purpose monitoring (seismic, geodetic, hydrogeologic), 7) low power consumption, 8) real time monitoring (connecting to sea bed cable), 9) accurate synchronization, 10) wide frequency range / high dynamic range ADC, 11) down sizing (installing into 9-5/8" casing with tubing), 12) system redundancy (fault tolerant). We started to develop an experimental prototype (EXP) for field test

  18. Effects of caffeine on time trial performance in sedentary men.

    PubMed

    Laurence, George; Wallman, Karen; Guelfi, Kym

    2012-01-01

    It is not known if ergogenic effects of caffeine ingestion in athletic groups occur in the sedentary. To investigate this, we used a counterbalanced, double-blind, crossover design to examine the effects of caffeine ingestion (6 mg · kg⁻¹ body-mass) on exercise performance, substrate utilisation and perceived exertion during 30 minutes of self-paced stationary cycling in sedentary men. Participants performed two trials, one week apart, after ingestion of either caffeine or placebo one hour before exercise. Participants were instructed to cycle as quickly as they could during each trial. External work (J · kg⁻¹) after caffeine ingestion was greater than after placebo (P = 0.001, effect size [ES] = 0.3). Further, heart rate, oxygen uptake and energy expenditure during exercise were greater after caffeine ingestion (P = 0.031, ES = 0.4; P = 0.009, ES = 0.3 and P = 0.018, ES = 0.3; respectively), whereas ratings of perceived exertion and respiratory exchange ratio values did not differ between trials (P = 0.877, ES = 0.1; P = 0.760, ES = 0.1; respectively). The ability to do more exercise after caffeine ingestion, without an accompanying increase in effort sensation, could motivate sedentary men to participate in exercise more often and so reduce adverse effects of inactivity on health.

  19. Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

    PubMed Central

    Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andrés; Bloch, Michael H.

    2013-01-01

    Objective To determine if there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method We conducted a meta-analysis of published and unpublished randomized, placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years old with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (< 3 years after study completion) versus delayed publication. Results We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ±1.9) than trials with positive findings (2.2 ±0.9; log-rank χ2 = 4.35, p = 0.037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI: 5 – 11) was significantly greater than those with delayed publication (17, 95% CI: 9 – ∞; χ2 = 4.98, p = 0.025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ±11.01) and negative results (7.54 ±7.90) did not statistically differ (t = 1.4, df = 10, p = 0.17). Conclusions Despite a small number of trials of SRIs for pediatric antidepressants we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing. PMID:21156271

  20. Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andres; Bloch, Michael H.

    2011-01-01

    Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main…

  1. Influence of accurate and inaccurate 'split-time' feedback upon 10-mile time trial cycling performance.

    PubMed

    Wilson, Mathew G; Lane, Andy M; Beedie, Chris J; Farooq, Abdulaziz

    2012-01-01

    The objective of the study is to examine the impact of accurate and inaccurate 'split-time' feedback upon a 10-mile time trial (TT) performance and to quantify power output into a practically meaningful unit of variation. Seven well-trained cyclists completed four randomised bouts of a 10-mile TT on a SRM™ cycle ergometer. TTs were performed with (1) accurate performance feedback, (2) without performance feedback, (3) and (4) false negative and false positive 'split-time' feedback showing performance 5% slower or 5% faster than actual performance. There were no significant differences in completion time, average power output, heart rate or blood lactate between the four feedback conditions. There were significantly lower (p < 0.001) average [Formula: see text] (ml min(-1)) and [Formula: see text] (l min(-1)) scores in the false positive (3,485 ± 596; 119 ± 33) and accurate (3,471 ± 513; 117 ± 22) feedback conditions compared to the false negative (3,753 ± 410; 127 ± 27) and blind (3,772 ± 378; 124 ± 21) feedback conditions. Cyclists spent a greater amount of time in a '20 watt zone' 10 W either side of average power in the negative feedback condition (fastest) than the accurate feedback (slowest) condition (39.3 vs. 32.2%, p < 0.05). There were no significant differences in the 10-mile TT performance time between accurate and inaccurate feedback conditions, despite significantly lower average [Formula: see text] and [Formula: see text] scores in the false positive and accurate feedback conditions. Additionally, cycling with a small variation in power output (10 W either side of average power) produced the fastest TT. Further psycho-physiological research should examine the mechanism(s) why lower [Formula: see text] and [Formula: see text] scores are observed when cycling in a false positive or accurate feedback condition compared to a false negative or blind feedback condition.

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

    PubMed

    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.

  3. Real-time prediction of clinical trial enrollment and event counts: A review.

    PubMed

    Heitjan, Daniel F; Ge, Zhiyun; Ying, Gui-Shuang

    2015-11-01

    Clinical trial planning involves the specification of a projected duration of enrollment and follow-up needed to achieve the targeted study power. If pre-trial estimates of enrollment and event rates are inaccurate, projections can be faulty, leading potentially to inadequate power or other mis-allocation of resources. Recent years have witnessed the development of methods that use the accumulating data from the trial itself to create improved predictions in real time. We review these methods, taking as a case study REMATCH, a trial that compared a left-ventricular assist device to optimal medical management in the treatment of end-stage heart failure. REMATCH provided the motivation and test bed for the first real-time clinical trial prediction model. Our review summarizes developments to date and points to unresolved issues and open research opportunities. PMID:26188165

  4. A reliable preloaded cycling time trial for use in conditions of significant thermal stress.

    PubMed

    Che Jusoh, M R; Morton, R H; Stannard, S R; Mündel, T

    2015-06-01

    The purpose of this study was to assess the reliability of a 15-min time trial preloaded with 45 min of fixed-intensity cycling under laboratory conditions of thermal stress. Eight trained cyclists/triathletes (41 ± 10 years, VO2 peak: 69 ± 8 mL/kg/min, peak aerobic power: 391 ± 72 W) completed three trials (the first a familiarization) where they cycled at ∼ 55% VO2 peak for 45 min followed by a 15-min time trial (∼75% VO2 peak) under conditions of significant thermal stress (WBGT: 26.7 ± 0.8 °C, frontal convective airflow: 20 km/h). Seven days separated the trials, which were conducted at the same time of day following 24 h of exercise and dietary control. Reliability increased when a familiarization trial was performed, with the resulting coefficient of variation and intraclass correlation coefficient of the work completed during the 15-min time trial, 3.6% and 0.96, respectively. Therefore, these results demonstrate a high level of reliability for a 15-min cycling time trial following a 45-min preload when performed under laboratory conditions of significant thermal stress using trained cyclists/triathletes.

  5. No difference found in time to publication by statistical significance of trial results: a methodological review

    PubMed Central

    Jefferson, L; Cooper, E; Hewitt, C; Torgerson, T; Cook, L; Tharmanathan, P; Cockayne, S; Torgerson, D

    2016-01-01

    Objective Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results. Design Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting Methodological review of four general medical journals. Participants Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures Time from trial completion to publication. Results The median time from trial completion to publication was 431 days (n = 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p = 0.32). Conclusion In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals. PMID:27757242

  6. Power Analysis for Trials with Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Jozwiak, Katarzyna; Moerbeek, Mirjam

    2012-01-01

    Studies on event occurrence aim to investigate if and when subjects experience a particular event. The timing of events may be measured continuously using thin precise units or discretely using time periods. The latter metric of time is often used in social science research and the generalized linear model (GLM) is an appropriate model for data…

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

    PubMed

    Peterman, James E; Lim, Allen C; Ignatz, Ryan I; Edwards, Andrew G; Byrnes, William C

    2015-01-01

    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 [Formula: see text] peak, lactate threshold (LT), and economy. [Formula: see text] peak ([Formula: see text]) 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.

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

    PubMed

    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) in Trec and Tskin. Typical pacing profiles were demonstrated; however, there was no interaction (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.

  9. Real Time in Situ Gamma Radiation Measurements of the Plume Evolution from the Full-Scale Radiological Dispersal Device Field Trials.

    PubMed

    Korpach, Ed; Berg, Rodney; Erhardt, Lorne; Lebel, Luke; Liu, Chuanlei

    2016-05-01

    During the Full-Scale Radiological Dispersal Device Field Trials carried out in Suffield in 2012, several suites of detection and sampling equipment were used to measure and characterize the explosive dispersal of the short half-life radioactive tracer Lanthanum-140 ((140)La). The equipment deployed included networks of in situ real-time radiation monitoring detectors providing measurements of different sensitivities and characteristics. A dense array of lower sensitivity detectors was established near field, ranging from 10 to 450 m from the detonation location. A sparser array of more sensitive detectors was established in the far field (150 m to 3.5 km from the detonation location). Each was used to collect and report the dose rate data from the radioactive plume passage with a sample time resolution of 1 s. The two systems went through independent calibrations and were compared and shown to be consistent with each other. The in situ gamma radiation measurements have allowed the movement and evolution of the plume to be described and to identify deposition rates and non-uniformities in the temporal shape of the plume. This knowledge could be applied for emergency planning guidance for the case of release of radioactive material by a radiological dispersive device. PMID:27023030

  10. The effect of a caffeinated mouth-rinse on endurance cycling time-trial performance.

    PubMed

    Doering, Thomas M; Fell, James W; Leveritt, Michael D; Desbrow, Ben; Shing, Cecilia M

    2014-02-01

    The purpose of this study was to investigate if acute caffeine exposure via mouth-rinse improved endurance cycling time-trial performance in well-trained cyclists. It was hypothesized that caffeine exposure at the mouth would enhance endurance cycling time-trial performance. Ten well-trained male cyclists (mean ± SD: 32.9 ± 7.5 years, 74.7 ± 5.3 kg, 176.8 ± 5.1cm, VO₂peak = 59.8 ± 3.5 ml·kg⁻¹·min⁻¹) completed two experimental time-trials following 24 hr of dietary and exercise standardization. A randomized, double-blind, placebo-controlled, cross-over design was employed whereby cyclists completed a time-trial in the fastest time possible, which was equivalent work to cycling at 75% of peak aerobic power output for 60 min. Cyclists were administered 25 ml mouth-rinses for 10 s containing either placebo or 35 mg of anhydrous caffeine eight times throughout the time-trial. Perceptual and physiological variables were recorded throughout. No significant improvement in time-trial performance was observed with caffeine (3918 ± 243 s) compared with placebo mouth-rinse (3940 ± 227 s). No elevation in plasma caffeine was detected due to the mouth-rinse conditions. Caffeine mouth-rinse had no significant effect on rating of perceived exertion, heart rate, rate of oxygen consumption or blood lactate concentration. Eight exposures of a 35 mg dose of caffeine at the buccal cavity for 10s does not significantly enhance endurance cycling time-trial performance, nor does it elevate plasma caffeine concentration. PMID:23980239

  11. The effect of a caffeinated mouth-rinse on endurance cycling time-trial performance.

    PubMed

    Doering, Thomas M; Fell, James W; Leveritt, Michael D; Desbrow, Ben; Shing, Cecilia M

    2014-02-01

    The purpose of this study was to investigate if acute caffeine exposure via mouth-rinse improved endurance cycling time-trial performance in well-trained cyclists. It was hypothesized that caffeine exposure at the mouth would enhance endurance cycling time-trial performance. Ten well-trained male cyclists (mean ± SD: 32.9 ± 7.5 years, 74.7 ± 5.3 kg, 176.8 ± 5.1cm, VO₂peak = 59.8 ± 3.5 ml·kg⁻¹·min⁻¹) completed two experimental time-trials following 24 hr of dietary and exercise standardization. A randomized, double-blind, placebo-controlled, cross-over design was employed whereby cyclists completed a time-trial in the fastest time possible, which was equivalent work to cycling at 75% of peak aerobic power output for 60 min. Cyclists were administered 25 ml mouth-rinses for 10 s containing either placebo or 35 mg of anhydrous caffeine eight times throughout the time-trial. Perceptual and physiological variables were recorded throughout. No significant improvement in time-trial performance was observed with caffeine (3918 ± 243 s) compared with placebo mouth-rinse (3940 ± 227 s). No elevation in plasma caffeine was detected due to the mouth-rinse conditions. Caffeine mouth-rinse had no significant effect on rating of perceived exertion, heart rate, rate of oxygen consumption or blood lactate concentration. Eight exposures of a 35 mg dose of caffeine at the buccal cavity for 10s does not significantly enhance endurance cycling time-trial performance, nor does it elevate plasma caffeine concentration.

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

    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

  15. Pacing strategies during a cycling time trial with simulated headwinds and tailwinds.

    PubMed

    Atkinson, G; Brunskill, A

    2000-10-01

    The aims of this study were to examine the effects of one self-selected and two enforced pacing strategies (constant and variable power output) on cycling performance during a time trial in which variable wind conditions were simulated. Seven male cyclists rode their own bicycles on a Computrainer cycle ergometer, which was programmed to simulate a 16.1 km time trial on a flat course with a 8.05 km h(-1) headwind in the first half of the race and a 8.05 km h(-1) tailwind in the second half of the race. Subjects rode an initial time trial (ITT) at a self-selected pace to the best of their ability. The mean power output from this trial was then used to calculate the pacing strategies in the subsequent two trials: Constant (C)--riders rode the whole time trial at this mean power output; and Variable (V)--riders rode the first headwind section at a power output 5% higher than the mean and then reduced the power output in the last 8.05 km so that the mean power output was the same as in the initial time trial and in trial C. Power output, heart rate and ratings of perceived exertion (RPE) were recorded every 1.61 km. Finish times, 8.05 km split times and blood lactate levels, pre- and post-exercise (to calculate delta lactate), were also recorded in each trial. In the ITT, riders chose a mean +/- SD power output of 267 +/- 56 W in the first 1.61 km which was 14% higher than the overall race mean +/- SD of 235 +/- 41 W. Power outputs then dropped to below the race mean after the first few kilometres. Mean +/- SD finish times in the C and V time trials were 1661 +/- 130 and 1659 +/- 135 s, respectively. These were significantly faster than the 1671 +/- 131 s recorded in the initial time trial (p = 0.009), even though overall mean power outputs were similar (234 - 235 W) between all trials (p = 0.26). Overall mean RPE and delta lactate were lowest in trial V (p < 0.05). Perceived exertion showed a pacing strategy by race split interaction (p < 0.0001), but it was not

  16. Pacing strategies during a cycling time trial with simulated headwinds and tailwinds.

    PubMed

    Atkinson, G; Brunskill, A

    2000-10-01

    The aims of this study were to examine the effects of one self-selected and two enforced pacing strategies (constant and variable power output) on cycling performance during a time trial in which variable wind conditions were simulated. Seven male cyclists rode their own bicycles on a Computrainer cycle ergometer, which was programmed to simulate a 16.1 km time trial on a flat course with a 8.05 km h(-1) headwind in the first half of the race and a 8.05 km h(-1) tailwind in the second half of the race. Subjects rode an initial time trial (ITT) at a self-selected pace to the best of their ability. The mean power output from this trial was then used to calculate the pacing strategies in the subsequent two trials: Constant (C)--riders rode the whole time trial at this mean power output; and Variable (V)--riders rode the first headwind section at a power output 5% higher than the mean and then reduced the power output in the last 8.05 km so that the mean power output was the same as in the initial time trial and in trial C. Power output, heart rate and ratings of perceived exertion (RPE) were recorded every 1.61 km. Finish times, 8.05 km split times and blood lactate levels, pre- and post-exercise (to calculate delta lactate), were also recorded in each trial. In the ITT, riders chose a mean +/- SD power output of 267 +/- 56 W in the first 1.61 km which was 14% higher than the overall race mean +/- SD of 235 +/- 41 W. Power outputs then dropped to below the race mean after the first few kilometres. Mean +/- SD finish times in the C and V time trials were 1661 +/- 130 and 1659 +/- 135 s, respectively. These were significantly faster than the 1671 +/- 131 s recorded in the initial time trial (p = 0.009), even though overall mean power outputs were similar (234 - 235 W) between all trials (p = 0.26). Overall mean RPE and delta lactate were lowest in trial V (p < 0.05). Perceived exertion showed a pacing strategy by race split interaction (p < 0.0001), but it was not

  17. Mouth rinsing with a carbohydrate solution does not influence cycle time trial performance in the heat.

    PubMed

    Watson, Phillip; Nichols, David; Cordery, Philip

    2014-09-01

    Ten endurance-trained males were recruited to examine the possible role of carbohydrate (CHO) receptors in the mouth influencing exercise performance in the heat. Volunteers completed an incremental test to exhaustion to determine peak oxygen uptake, a familiarisation trial, followed by 2 experimental trials. Trials consisted of a 1-h time trial undertaken in a climatic chamber maintained at 30 °C, 60% relative humidity. Immediately before, and at regular intervals throughout exercise, subjects ingested a bolus of water and then were provided with either a placebo (PLA) or a 6.4% glucose (CHO) solution to rinse in the mouth for 10 s before being expectorated. There was no difference in total work done between the PLA and CHO trials (758.8 ± 149.0 kJ; 762.6 ± 141.1 kJ; P = 0.951). Pacing was also similar, with no differences in power output apparent during the experimental trials (P = 0.546). Core temperature (P = 0.615), heart rate (P = 0.505), ratings of perceived exertion (P = 0.181), and perceived thermal stress (P = 0.416) were not influenced by the nature of the intervention. Blood glucose concentrations were similar during the CHO and PLA trials (P = 0.117). In contrast to the findings of several studies undertaken in temperate conditions, the present investigation failed to support role of oral sensing of CHO in influencing performance during prolonged exercise in warm conditions. PMID:25154896

  18. Mouth rinsing with a carbohydrate solution does not influence cycle time trial performance in the heat.

    PubMed

    Watson, Phillip; Nichols, David; Cordery, Philip

    2014-09-01

    Ten endurance-trained males were recruited to examine the possible role of carbohydrate (CHO) receptors in the mouth influencing exercise performance in the heat. Volunteers completed an incremental test to exhaustion to determine peak oxygen uptake, a familiarisation trial, followed by 2 experimental trials. Trials consisted of a 1-h time trial undertaken in a climatic chamber maintained at 30 °C, 60% relative humidity. Immediately before, and at regular intervals throughout exercise, subjects ingested a bolus of water and then were provided with either a placebo (PLA) or a 6.4% glucose (CHO) solution to rinse in the mouth for 10 s before being expectorated. There was no difference in total work done between the PLA and CHO trials (758.8 ± 149.0 kJ; 762.6 ± 141.1 kJ; P = 0.951). Pacing was also similar, with no differences in power output apparent during the experimental trials (P = 0.546). Core temperature (P = 0.615), heart rate (P = 0.505), ratings of perceived exertion (P = 0.181), and perceived thermal stress (P = 0.416) were not influenced by the nature of the intervention. Blood glucose concentrations were similar during the CHO and PLA trials (P = 0.117). In contrast to the findings of several studies undertaken in temperate conditions, the present investigation failed to support role of oral sensing of CHO in influencing performance during prolonged exercise in warm conditions.

  19. Conductive and evaporative precooling lowers mean skin temperature and improves time trial performance in the heat.

    PubMed

    Faulkner, S H; Hupperets, M; Hodder, S G; Havenith, G

    2015-06-01

    Self-paced endurance performance is compromised by moderate-to-high ambient temperatures that are evident in many competitive settings. It has become common place to implement precooling prior to competition in an attempt to alleviate perceived thermal load and performance decline. The present study aimed to investigate precooling incorporating different cooling avenues via either evaporative cooling alone or in combination with conductive cooling on cycling time trial performance. Ten trained male cyclists completed a time trial on three occasions in hot (35 °C) ambient conditions with the cooling garment prepared by (a) immersion in water (COOL, evaporative); (b) immersion in water and frozen (COLD, evaporative and conductive); or (c) no precooling (CONT). COLD improved time trial performance by 5.8% and 2.6% vs CONT and COOL, respectively (both P < 0.05). Power output was 4.5% higher for COLD vs CONT (P < 0.05). Mean skin temperature was lower at the onset of the time trial following COLD compared with COOL and CONT (both P < 0.05) and lasted for the first 20% of the time trial. Thermal sensation was perceived cooler following COOL and COLD. The combination of evaporative and conductive cooling (COLD) had the greatest benefit to performance, which is suggested to be driven by reduced skin temperature following cooling.

  20. Real-time monitoring for human clinical trials

    SciTech Connect

    Harker, Y.D.

    1995-11-01

    On August 3-4, 1994, an INEL team made measurements related to a real-time monitoring system for use on the epithermal beam facility at the BMRR. BNL has installed two fission chambers in front of the beam collimator, which are to monitor the beam coming from the reactor. These two monitors are located with one just above the 16-cm dia. front aperture and the other is just below. The fission chambers contain depleted uranium, but because of the small amount of U-235 present, they respond to thermal and near thermal neutrons rather than fast neutrons. This feature combined with their relatively small size (0.6 cm dia x 4 cm long) makes them very good monitors in the BMRR epithermal neutron beam. The INEL team worked with H.B. Lui (BNL) in performing initial tests of these monitors and established the settings to achieve stable operation. The main purpose of the measurement studies was to establish a basis for a monitoring method that tracks the dose the patient is receiving rather than the neutron fluence being delivered down the beam line.

  1. Effect of Time of Day on Performance, Hormonal and Metabolic Response during a 1000-M Cycling Time Trial

    PubMed Central

    Fernandes, Alan Lins; Lopes-Silva, João Paulo; Bertuzzi, Rômulo; Casarini, Dulce Elena; Arita, Danielle Yuri; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    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, p<0.05), but there was no significant different in pacing. However, oxygen uptake and aerobic mechanical power output at 600 and 1000 m tended to be higher in the evening (p<0.07 and 0.09, respectively). There was also a main effect of time of day for insulin, cortisol, and total and free testosterone concentration, which were all higher in the morning (+60%, +26%, +31% and +22%, respectively, p<0.05). The growth hormone, was twofold higher in the evening (p<0.05). The plasma glucose was ∼11% lower in the morning (p<0.05). Glucagon, norepinephrine, epinephrine and lactate were similar for the morning and evening trials (p>0.05), but the norepinephrine response to the exercise was increased in the morning (+46%, p<0.05), and it was accompanied by a 5-fold increase in the response of glucose. Muscle recruitment, as measured by electromyography, was similar between morning and evening trials (p>0.05). Our findings suggest that performance was improved in the evening, and it was accompanied by an improved hormonal and metabolic milieu. PMID:25289885

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

    PubMed

    Fernandes, Alan Lins; Lopes-Silva, João Paulo; Bertuzzi, Rômulo; Casarini, Dulce Elena; Arita, Danielle Yuri; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    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, p<0.05), but there was no significant different in pacing. However, oxygen uptake and aerobic mechanical power output at 600 and 1000 m tended to be higher in the evening (p<0.07 and 0.09, respectively). There was also a main effect of time of day for insulin, cortisol, and total and free testosterone concentration, which were all higher in the morning (+60%, +26%, +31% and +22%, respectively, p<0.05). The growth hormone, was twofold higher in the evening (p<0.05). The plasma glucose was ∼11% lower in the morning (p<0.05). Glucagon, norepinephrine, epinephrine and lactate were similar for the morning and evening trials (p>0.05), but the norepinephrine response to the exercise was increased in the morning (+46%, p<0.05), and it was accompanied by a 5-fold increase in the response of glucose. Muscle recruitment, as measured by electromyography, was similar between morning and evening trials (p>0.05). Our findings suggest that performance was improved in the evening, and it was accompanied by an improved hormonal and metabolic milieu.

  3. Longitudinal Clinical Trials with Adaptive Choice of Follow-up Time

    PubMed Central

    Jeffries, Neal O.; Geller, Nancy L.

    2015-01-01

    Summary In longitudinal studies comparing two treatments with a maximum follow-up time there may be interest in examining treatment effects for intermediate follow-up times. One motivation may be to identify the time period with greatest treatment difference when there is a non-monotone treatment effect over time; another motivation may be to make the trial more efficient in terms of time to reach a decision on whether a new treatment is efficacious or not. Here we test the composite null hypothesis of no difference at any follow-up time versus the alternative that there is a difference at at least one follow-up time. The methods are applicable when a few measurements are taken over time, such as in early longitudinal trials or in ancillary studies. Suppose the test statistic Ztk will be used to test the hypothesis of no treatment effect at a fixed follow-up time tk. In this context a common approach is to perform a pilot study on N1 subjects, and evaluate the treatment effect at the fixed time points t1, …, tK and choose t* as the value of tk for which Ztk is maximized. Having chosen t* a second trial can be designed. In a setting with group sequential testing we consider several adaptive alternatives to this approach that treat the pilot and second trial as a seamless, combined entity and evaluate Type I error and power characteristics. The adaptive designs we consider typically have improved power over the common, separate trial approach. PMID:25818116

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

    PubMed Central

    Peterman, James E.; Lim, Allen C.; Ignatz, Ryan I.; Edwards, Andrew G.

    2015-01-01

    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 \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\dot {V}{O}_{2}$\\end{document}V˙O2 peak, lactate threshold (LT), and economy. \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\dot {V}{O}_{2}$\\end{document}V˙O2 peak (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mathrm{l}~\\min ^{-1}$\\end{document}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

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

    PubMed Central

    Kaplan, Robert M.; Irvin, Veronica L.

    2015-01-01

    Background We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time. Methods 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. Results 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. Conclusions 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. PMID:26244868

  6. Effect of repeated sodium phosphate loading on cycling time-trial performance and VO2peak.

    PubMed

    Brewer, Cameron P; Dawson, Brian; Wallman, Karen E; Guelfi, Kym J

    2013-04-01

    Research into supplementation with sodium phosphate has not investigated the effects of a repeated supplementation phase. Therefore, this study examined the potential additive effects of repeated sodium phosphate (SP) supplementation on cycling time-trial performance and peak oxygen uptake (VO2peak). Trained male cyclists (N = 9, M ± SD VO2peak = 65.2 ± 4.8 ml · kg-1 · min-1) completed baseline 1,000-kJ time-trial and VO2peak tests separated by 48 hr, then ingested either 50 mg · kg fat-free mass-1 · d-1 of tribasic SP or a combined glucose and NaCl placebo for 6 d before performing these tests again. A 14-d washout period separated the end of one loading phase and the start of the next, with 2 SP and 1 placebo phase completed in a counterbalanced order. Although time-trial performance (55.3-56.5 min) was shorter in SP1 and SP2 (~60-70 s), effect sizes and smallest-worthwhile-change values did not differ in comparison with baseline and placebo. However, mean power output was greater than placebo during time-trial performance at the 250-kJ and 500-kJ time points (p < .05) after the second SP phase. Furthermore, mean VO2peak values (p < .01) were greater after the SP1 (3.5-4.3%), with further improvements (p < .01) found in SP2 (7.1-7.7%), compared with baseline and placebo. In summary, repeated SP supplementation, ingested either 15 or 35 d after initial loading, can have an additive effect on VO2peak and possibly time-trial performance.

  7. Syllable-Timed Speech Treatment for School-Age Children Who Stutter: A Phase I Trial

    ERIC Educational Resources Information Center

    Andrews, Cheryl; O'Brian, Sue; Harrison, Elisabeth; Onslow, Mark; Packman, Ann; Menzies, Ross

    2012-01-01

    Purpose: This clinical trial determined the outcomes of a simple syllable-timed speech (STS) treatment for school-age children who stutter. Method: Participants were 10 children, ages 6-11 years, who stutter. Treatment involved training the children and their parents to use STS at near normal speech rates. The technique was practiced in the clinic…

  8. Effects of Time between Trials on Rats' and Pigeons' Choices with Probabilistic Delayed Reinforcers

    ERIC Educational Resources Information Center

    Mazur, James E.; Biondi, Dawn R.

    2011-01-01

    Parallel experiments with rats and pigeons examined reasons for previous findings that in choices with probabilistic delayed reinforcers, rats' choices were affected by the time between trials whereas pigeons' choices were not. In both experiments, the animals chose between a standard alternative and an adjusting alternative. A choice of the…

  9. A comparison of caffeine versus pseudoephedrine on cycling time-trial performance.

    PubMed

    Spence, Angela L; Sim, Marc; Landers, Grant; Peeling, Peter

    2013-10-01

    Both caffeine (CAF) and pseudoephedrine (PSE) are proposed to be central nervous system stimulants. However, during competition, CAF is a permitted substance, whereas PSE is a banned substance at urinary levels >150 μg · ml(-1). As a result, this study aimed to compare the effect of CAF versus PSE use on cycling time trial (TT) performance to explore whether the legal stimulant was any less ergogenic than the banned substance. Here, 10 well-trained male cyclists or triathletes were recruited for participation. All athletes were required to attend the laboratory on four separate occasions--including a familiarization trial and three experimental trials, which required participants to complete a simulated 40 km (1,200 kJ) cycling TT after the ingestion of either 200 mg CAF, 180 mg PSE or a nonnutritive placebo (PLA). The results showed that the total time taken and the mean power produced during each TT was not significantly different (p > .05) between trials, despite a 1.3% faster overall time (~57 s) after CAF consumption. Interestingly, the time taken to complete the second half of the TT was significantly faster (p < .05) in CAF as compared with PSE (by 99 s), with magnitude based inferences suggesting a 91% beneficial effect of CAF during the second half of the TT. This investigation further confirms the ergogenic benefits of CAF use during TT performances and further suggests this legal CNS stimulant has a better influence than a supra-therapeutic dose of PSE.

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

    PubMed

    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), no significant change was seen following lactate ingestion (p > 0.05). Subjects in the LACTATE condition did have a significantly higher heart rate (p < 0.05) without experiencing any greater perceived exertion (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.

  11. Uncertainty of trial timing enhances acquisition of conditioned eyeblinks in anxiety vulnerable individuals.

    PubMed

    Allen, M T; Myers, C E; Servatius, R J

    2016-05-01

    Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean=30+/- 5s), a long ITI (mean=57+/- 5s) or a variable long ITI (mean=57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals. PMID:26873040

  12. Uncertainty of trial timing enhances acquisition of conditioned eyeblinks in anxiety vulnerable individuals.

    PubMed

    Allen, M T; Myers, C E; Servatius, R J

    2016-05-01

    Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean=30+/- 5s), a long ITI (mean=57+/- 5s) or a variable long ITI (mean=57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals.

  13. Time Regained: When People Stop a Physical Activity Program, How Does Their Time Use Change? A Randomised Controlled Trial

    PubMed Central

    Gomersall, Sjaan; Maher, Carol; English, Coralie; Rowlands, Alex; Olds, Tim

    2015-01-01

    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. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID

  14. Information mining over heterogeneous and high-dimensional time-series data in clinical trials databases.

    PubMed

    Altiparmak, Fatih; Ferhatosmanoglu, Hakan; Erdal, Selnur; Trost, Donald C

    2006-04-01

    An effective analysis of clinical trials data involves analyzing different types of data such as heterogeneous and high dimensional time series data. The current time series analysis methods generally assume that the series at hand have sufficient length to apply statistical techniques to them. Other ideal case assumptions are that data are collected in equal length intervals, and while comparing time series, the lengths are usually expected to be equal to each other. However, these assumptions are not valid for many real data sets, especially for the clinical trials data sets. An addition, the data sources are different from each other, the data are heterogeneous, and the sensitivity of the experiments varies by the source. Approaches for mining time series data need to be revisited, keeping the wide range of requirements in mind. In this paper, we propose a novel approach for information mining that involves two major steps: applying a data mining algorithm over homogeneous subsets of data, and identifying common or distinct patterns over the information gathered in the first step. Our approach is implemented specifically for heterogeneous and high dimensional time series clinical trials data. Using this framework, we propose a new way of utilizing frequent itemset mining, as well as clustering and declustering techniques with novel distance metrics for measuring similarity between time series data. By clustering the data, we find groups of analytes (substances in blood) that are most strongly correlated. Most of these relationships already known are verified by the clinical panels, and, in addition, we identify novel groups that need further biomedical analysis. A slight modification to our algorithm results an effective declustering of high dimensional time series data, which is then used for "feature selection." Using industry-sponsored clinical trials data sets, we are able to identify a small set of analytes that effectively models the state of normal health.

  15. Optimal designs in longitudinal trials with varying treatment effects and discrete-time survival endpoints.

    PubMed

    Safarkhani, Maryam; Moerbeek, Mirjam

    2015-09-30

    It is plausible to assume that the treatment effect in a longitudinal study will vary over time. It can become either stronger or weaker as time goes on. Here, we extend previous work on optimal designs for discrete-time survival analysis to trials with the treatment effect varying over time. In discrete-time survival analysis, subjects are measured in discrete time intervals, while they may experience the event at any point in time. We focus on studies where the width of time intervals is fixed beforehand, meaning that subjects are measured more often when the study duration increases. The optimal design is defined as the optimal combination of the number of subjects, the number of measurements for each subject, and the optimal proportion of subjects assigned to the experimental condition. We study optimal designs for different optimality criteria and linear cost functions. We illustrate the methodology of finding optimal designs using a clinical trial that studies the effect of an outpatient mental health program on reducing substance abuse among patients with severe mental illness. We observe that optimal designs depend to some extent on the rate at which group differences vary across time intervals and the direction of these changes over time. We conclude that an optimal design based on the assumption of a constant treatment effect is not likely to be efficient if the treatment effect varies across time. PMID:26179808

  16. Efficient Bayesian Joint Models for Group Randomized Trials with Multiple Observation Times and Multiple Outcomes

    PubMed Central

    Xu, Xinyi; Pennell, Michael L.; Lu, Bo; Murray, David M.

    2013-01-01

    Summary In this paper, we propose a Bayesian method for Group Randomized Trials (GRTs) with multiple observation times and multiple outcomes of different types. We jointly model these outcomes using latent multivariate normal linear regression, which allows treatment effects to change with time and accounts for 1.) intra-class correlation (ICC) within groups 2.) the correlation between different outcomes measured on the same subject and 3.) the over-time correlation (OTC) of each outcome. Moreover we develop a set of innovative priors for the variance components which yield direct inference on the correlations, avoid undesirable constraints, and allow utilization of information from previous studies. We illustrate through simulations that our model can improve estimation efficiency (lower posterior standard deviations) of ICCs and treatment effects relative to single outcome models and models with diffuse priors on the variance components. We also demonstrate the methodology using body composition data collected in the Trial of Activity in Adolescent Girls (TAAG). PMID:22733563

  17. Effect of different aerodynamic time trial cycling positions on muscle activation and crank torque.

    PubMed

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

    2016-05-01

    To reduce air resistance, time trial cyclists and triathletes lower their torso angle. The aim of this study was to investigate the effect of lowering time trial torso angle positions on muscle activation patterns and crank torque coordination. It was hypothesized that small torso angles yield a forward shift of the muscle activation timing and crank torque. Twenty-one trained cyclists performed three exercise bouts at 70% maximal aerobic power in a time trial position at three different torso angles (0°, 8°, and 16°) at a fixed cadence of 85 rpm. Measurements included surface electromyography, crank torques and gas exchange. A significant increase in crank torque range and forward shift in peak torque timing was found at smaller torso angles. This relates closely with the later onset and duration of the muscle activation found in the gluteus maximus muscle. Torso angle effects were only observed in proximal monoarticular muscles. Moreover, all measured physiological variables (oxygen consumption, breathing frequency, minute ventilation) were significantly increased with lowering torso angle and hence decreased the gross efficiency. The findings provide support for the notion that at a cycling intensity of 70% maximal aerobic power, the aerodynamic gains outweigh the physiological/biomechanical disadvantages in trained cyclists.

  18. Physiological and Anthropometrical Predictors of 15-Kilometer Time Trial Cycling Performance Time.

    ERIC Educational Resources Information Center

    Miller, Frank R.; Manfredi, Thomas G.

    1987-01-01

    A study assessing the relationship between physiological and anthropometrical variables and cycling performance time found that anaerobic threshhold and body circumference ratio correlated highly with cycling performance time. (Author/CB)

  19. The Surface Mass Balance of the Antarctic Peninsula at 5.5 km horizontal resolution, as simulated by a regional atmospheric climate model

    NASA Astrophysics Data System (ADS)

    van Wessem, M.; Reijmer, C.; van den Broeke, M. R.; Ligtenberg, S.; Scambos, T. A.; Barrand, N. E.; Van De Berg, W. J.; Thomas, E. R.; Wuite, J.; van Meijgaard, E.; Turner, J.

    2015-12-01

    The Antarctic Peninsula (AP) is one of the most rapidly changing regions on earth, but limited detailed information is available about AP climate due to a lack of observational data. Here, we present a high-resolution (5.5 km) estimate of the surface mass balance (SMB) for the AP, from 1979 to 2014, calculated by the regional atmospheric climate model RACMO2.3, that is specifically adapted for use over the polar regions. Next to this, a firn densification model is used to calculate the processes in the snowpack, such as firn compaction and meltwater percolation, refreezing, and runoff. A comparison with the few available in-situ observations shows that the AP SMB is well modeled, but that discrepancies remain that are mainly related to the highly variable AP topography compared to the model resolution. Integrated over an ice sheet area of 4.1 105 km2, the climatological (1979-2014) SMB of the AP amounts to 351 Gt y-1 (with interannual variability = 58 Gt y-1), which mostly consists of snowfall (363 ± 56 Gt y-1). The other SMB components, sublimation, drifting snow erosion and meltwater runoff, are small (11, 0.5 and 4 Gt y-1, respectively). The AP mountains act as an important climate barrier, leading to distinct differences between the climate of the western AP (WAP) and the eastern AP (EAP). For instance, 77% of all AP snowfall falls over the WAP, where strong orographic forcing leads to snowfall rates >4 m w.e. y-1 on the northwestern slopes, while snowfall rates are <400 mm w.e. y-1 over the EAP ice shelves. These results, and further investigations of this sharp west-to-east climate distinction, clearly highlight the different forcing mechanisms of the SMB over the WAP and the EAP: over the WAP most snowfall is orographically induced, while over the EAP it is generated by depressions over the Weddell Sea. Furthermore, no significant trends are found in any of the SMB components, except for a slight decrease in snowmelt.

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

    PubMed

    Kim, Sungshin; Oh, Youngmin; Schweighofer, Nicolas

    2015-01-01

    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. PMID:26599075

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

    PubMed

    Kim, Sungshin; Oh, Youngmin; Schweighofer, Nicolas

    2015-01-01

    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.

  2. Doubling of muscle carnosine concentration does not improve laboratory 1-hr cycling time-trial performance.

    PubMed

    Chung, Weiliang; Baguet, Audrey; Bex, Tine; Bishop, David J; Derave, Wim

    2014-06-01

    Muscle carnosine loading through chronic oral beta-alanine supplementation has been shown to be effective for short-duration, high-intensity exercise. This randomized, placebo-controlled study explored whether the ergogenic effect of beta-alanine supplementation is also present for longer duration exercise. Subjects (27 well-trained cyclists/triathletes) were supplemented with either beta-alanine or placebo (6.4 g/day) for 6 weeks. Time to completion and physiological variables for a 1-hr cycling time-trial were compared between preand postsupplementation. Muscle carnosine concentration was also assessed via proton magnetic resonance spectroscopy before and after supplementation. Following beta-alanine supplementation, muscle carnosine concentration was increased by 143 ± 151% (mean ± SD; p < .001) in the gastrocnemius and 161 ± 56% (p < .001) in the soleus. Postsupplementation time trial performance was significantly slower in the placebo group (60.6 ± 4.4-63.0 ± 5.4 min; p < .01) and trended toward a slower performance following beta-alanine supplementation (59.8 ± 2.8-61.7 ± 3.0 min; p = .069). We found an increase in lactate/proton concentration ratio following beta-alanine supplementation during the time-trial (209.0 ± 44.0 (beta-alanine) vs. 161.9 ± 54.4 (placebo); p < .05), indicating that a similar lactate concentration was accompanied by a lower degree of systemic acidosis, even though this acidosis was quite moderate (pH ranging from 7.30 to 7.40). In conclusion, chronic beta-alanine supplementation in well-trained cyclists had a very pronounced effect on muscle carnosine concentration and a moderate attenuating effect on the acidosis associated with lactate accumulation, yet without affecting 1-h time-trial performance under laboratory conditions.

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

    PubMed

    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.

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

    PubMed

    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. PMID:25285468

  5. The Hydrothermal Vent Biosampler (HVB) Developed to Collect `Pristine' Samples (<6.5km depth, 400C, 0.2u pore) for Microbial Analyses. It's use in Eyjafjordur Fjord, Iceland & Myojin Knoll & Planned deployment on the Myojin Knoll & Suiyo Seamount.

    NASA Astrophysics Data System (ADS)

    Behar, A.; Bruckner, J.; Venkateswaran, K.; Matthews, J.

    2006-12-01

    Marine hydrothermal systems and the unique biota associated with them represent some of the most interesting ecosystems on the planet. These `extreme' environments are often composed of vents spewing super-heated fluid containing a variety of minerals and reduced compounds, numerous of which can be used as substrates for growth by microorganisms. To accurately describe the diversity and distribution of these chemosynthetic communities, it is essential to collect samples from defined locations associated with a given hydrothermal vent without contamination from the surrounding water column (e.g. the collected samples are `pristine'). Additionally, samples need to be collected in sufficient volume to a) account for the potential low biomass of these environments and b) provide modern molecular techniques with adequate sample material. The hydrothermal vent biosampler (HVB) was developed to collect `pristine' hydrothermal vent samples for microbial analyses. Utilizing an array of sensors (temperature monitors and flow meters), the system can relay real time data regarding sampling conditions allowing accurate placement of the HVB's collection nozzle and ensuring samples are collected from defined locations. The unit has been designed to withstand extreme conditions (source water temperatures >400°C) and has been pressure tested to a simulated depth of 6.5km and undergone field trials along the Eyjafjordur Fjord hydrothermal system (Iceland). Collection of sufficient biomass is achieved through employment of a series of filters (90, 60, 7 and 0.2 ìm pore sizes) that concentrate ~20L of hydrothermal fluid to a final volume of 500-ml. Filtered samples can be directly collected from the HVB for subsequent biological analyses (both culture- and molecular-based). In conjunction with JAMSTEC, further field exercises along the Myojin Knoll and Suiyo Seamount have been planned for November 2006.

  6. Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials

    PubMed Central

    Goldstein, J L; Chan, F K L; Lanas, A; Wilcox, C M; Peura, D; Sands, G H; Berger, M F; Nguyen, H; Scheiman, J M

    2011-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events. Aim To evaluate the incidence and time to a clinically meaningful decrease in haemoglobin in two double-blind, prospective randomised clinical trials comparing NSAIDs in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Methods In CLASS, patients with OA/RA who were aged ≥18 years and required continuous NSAID treatment were included; patients who were Helicobacter pylori positive and/or using aspirin were not excluded. In contrast, in the CONDOR trial, comparing celecoxib alone to diclofenac sustained release (plus omeprazole), patients were aged ≥60 years or ≥18 years with a history of gastroduodenal ulcer and were H. pylori negative; aspirin or other anti-platelet users were excluded. To make a parallel post hoc analysis we limited our study to 6 months and the populations to only the non-aspirin users in CLASS and those patients receiving either celecoxib or diclofenac. A decrease in haemoglobin of ≥2 g/dL defined the primary end point. Results At 6 months, in the CLASS and CONDOR trials, 1.9% and 2.0% of patients treated with celecoxib and 3.3% and 5.7% of patients treated with diclofenac developed a ≥2 g/dL decrease in haemoglobin, respectively, [CLASS: odds ratio (OR) 1.80 (95% confidence interval (CI), 1.22–2.65) and CONDOR: OR 2.93 (95% CI, 2.06–4.15), respectively]. Conclusion In these two large, independent trials, clinically-meaningful decreases in haemoglobin ≥2 g/dL occurred in a relatively similar fashion over time despite differences in trial designs. PMID:21810115

  7. Variability of single trial brain activation predicts fluctuations in reaction time.

    PubMed

    Bender, Stephan; Banaschewski, Tobias; Roessner, Veit; Klein, Christoph; Rietschel, Marcella; Feige, Bernd; Brandeis, Daniel; Laucht, Manfred

    2015-03-01

    Brain activation stability is crucial to understanding attention lapses. EEG methods could provide excellent markers to assess neuronal response variability with respect to temporal (intertrial coherence) and spatial variability (topographic consistency) as well as variations in activation intensity (low frequency variability of single trial global field power). We calculated intertrial coherence, topographic consistency and low frequency amplitude variability during target P300 in a continuous performance test in 263 15-year-olds from a cohort with psychosocial and biological risk factors. Topographic consistency and low frequency amplitude variability predicted reaction time fluctuations (RTSD) in a linear model. Higher RTSD was only associated with higher psychosocial adversity in the presence of the homozygous 6R-10R dopamine transporter haplotype. We propose that topographic variability of single trial P300 reflects noise as well as variability in evoked cortical activation patterns. Dopaminergic neuromodulation interacted with environmental and biological risk factors to predict behavioural reaction time variability.

  8. Analysis of Time to Event Outcomes in Randomized Controlled Trials by Generalized Additive Models

    PubMed Central

    Argyropoulos, Christos; Unruh, Mark L.

    2015-01-01

    Background 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. Methods 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. Findings 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. Conclusions 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

  9. Timing is everything? Reconciling the results of recent trials in acute kidney injury.

    PubMed

    Wyatt, Christina M; Coca, Steven G

    2016-10-01

    Observational studies have failed to establish the optimal timing of renal replacement therapy in critically ill adults with acute kidney injury, with some studies suggesting benefit and others suggesting the potential for harm with earlier initiation. Two recent randomized trials have addressed this controversy, also with conflicting results. Careful consideration of differences between the 2 studies is essential when applying the results to clinical practice in the intensive care unit. PMID:27575558

  10. Carbohydrate Mouth Rinsing Enhances High Intensity Time Trial Performance Following Prolonged Cycling

    PubMed Central

    Luden, Nicholas D.; Saunders, Michael J.; D’Lugos, Andrew C.; Pataky, Mark W.; Baur, Daniel A.; Vining, Caitlin B.; Schroer, Adam B.

    2016-01-01

    There is good evidence that mouth rinsing with carbohydrate (CHO) solutions can enhance endurance performance (≥30 min). The impact of a CHO mouth rinse on sprint performance has been less consistent, suggesting that CHO may confer benefits in conditions of ‘metabolic strain’. To test this hypothesis, the current study examined the impact of late-exercise mouth rinsing on sprint performance. Secondly, we investigated the effects of a protein mouth rinse (PRO) on performance. Eight trained male cyclists participated in three trials consisting of 120 min of constant-load cycling (55% Wmax) followed by a 30 km computer-simulated time trial, during which only water was provided. Following 15 min of muscle function assessment, 10 min of constant-load cycling (3 min at 35% Wmax, 7 min at 55% Wmax) was performed. This was immediately followed by a 2 km time trial. Subjects rinsed with 25 mL of CHO, PRO, or placebo (PLA) at min 5:00 and 14:30 of the 15 min muscle function phase, and min 8:00 of the 10-min constant-load cycling. Magnitude-based inferential statistics were used to analyze the effects of the mouth rinse on 2-km time trial performance and the following physiological parameters: Maximum Voluntary Contract (MVC), Rating of Perceived Exertion (RPE), Heart Rate (HR), and blood glucose levels. The primary finding was that CHO ‘likely’ enhanced performance vs. PLA (3.8%), whereas differences between PRO and PLA were unclear (0.4%). These data demonstrate that late-race performance is enhanced by a CHO rinse, but not PRO, under challenging metabolic conditions. More data should be acquired before this strategy is recommended for the later stages of cycling competition under more practical conditions, such as when carbohydrates are supplemented throughout the preceding minutes/hours of exercise. PMID:27657117

  11. Effect of age on 16.1-km time-trial performance.

    PubMed

    Balmer, James; Bird, Steve; Davison, Richard; Lucia, Alejandro

    2008-01-15

    In this study, we assessed the performance of trained senior (n = 6) and veteran (n = 6) cyclists (mean age 28 years, s = 3 and 57 years, s = 4 respectively). Each competitor completed two cycling tests, a ramped peak aerobic test and an indoor 16.1-km time-trial. The tests were performed using a Kingcycle ergometer with the cyclists riding their own bicycle fitted with an SRM powermeter. Power output, heart rate, and gas exchange variables were recorded continuously and blood lactate concentration [HLa] was assessed 3 min after the peak ramped test and at 2.5-min intervals during the time-trial. Peak values for power output (RMP(max)), heart rate (HR(peak)), oxygen uptake (VO2(peak)), and ventilation (V(Epeak)) attained during the ramped test were higher in the senior group (P < 0.05), whereas [HLa](peak), RER(peak), V(E): VO2(peak), and economy(peak) were similar between groups (P > 0.05). Time-trial values (mean for duration of race) for power output (W(TT)), heart rate (HR(TT)), VO2 (VO(2TT)), and V(E) (V(ETT)) were higher in the seniors (P < 0.05), but [HLa](TT), RER(TT), V(ETT): VO2(TT), and economy(TT) were similar between the groups (P > 0.05). Time-trial exercise intensity, expressed as %RMP(max), %HR(peak), % VO2(peak), and % V(Epeak), was similar (P > 0.05) for seniors and veterans (W(TT): 81%, s = 2 vs. 78%, s = 8; HR(TT): 96%, s = 4 vs. 94%, s = 4; VO2(TT): 92%, s = 4 vs. 95%, s = 10; V(ETT): 89%, s = 8 vs. 85%, s = 8, respectively). Overall, seniors attained higher absolute values for power output, heart rate, VO2, and V(E) but not blood lactate concentration, respiratory exchange ratio (RER), V(E): VO2, and economy. Veterans did not accommodate age-related declines in time trial performance by maintaining higher relative exercise intensity.

  12. The Effects of Caffeinated “Energy Shots” on Time Trial Performance

    PubMed Central

    Schubert, Matthew Mark; Astorino, Todd Anthony; Azevedo, John Leal

    2013-01-01

    An emerging trend in sports nutrition is the consumption of energy drinks and “energy shots”. Energy shots may prove to be a viable pre-competition supplement for runners. Six male runners (mean ± SD age and VO2max: 22.5 ± 1.8 years and 69.1 ± 5.7 mL·kg−1·min−1) completed three trials [placebo (PLA; 0 mg caffeine), Guayakí Yerba Maté Organic Energy Shot™ (YM; 140 mg caffeine), or Red Bull Energy Shot™ (RB; 80 mg caffeine)]. Treatments were ingested following a randomized, placebo-controlled crossover design. Participants ran a five kilometer time trial on a treadmill. No differences (p > 0.05) in performance were detected with RB (17.55 ± 1.01 min) or YM ingestion (17.86 ± 1.59 min) compared to placebo (17.44 ± 1.25 min). Overall, energy shot ingestion did not improve time-trial running performance in trained runners. PMID:23743969

  13. Performance during a 20-km cycling time-trial after caffeine ingestion

    PubMed Central

    2014-01-01

    Background The objective of this study was to analyze the effect of caffeine ingestion on the performance and physiological variables associated with fatigue in 20-km cycling time trials. Methods In a double-blind placebo-controlled crossover study, 13 male cyclists (26 ± 10 y, 71 ± 9 kg, 176 ± 6 cm) were randomized into 2 groups and received caffeine (CAF) capsules (6 mg.kg−1) or placebo (PLA) 60 min before performing 20-km time trials. Distance, speed, power, rpm, rating of perceived exertion (RPE), electromyography (EMG) of the quadriceps muscles and heart rate (HR) were continuously measured during the tests. In addition, BRUMS questionnaire was applied before and after the tests. Results Significant interactions were found in power and speed (P = 0.001), which were significantly higher at the end of the test (final 2 km) after CAF condition. A main effect of time (P = 0.001) was observed for RPE and HR, which increased linearly until the end of exercise in both conditions. The time taken to complete the test was similar in both conditions (PLA = 2191 ± 158 s vs. CAF = 2181 ± 194 s, P = 0.61). No significant differences between CAF and PLA conditions were identified for speed, power, rpm, RPE, EMG, HR, and BRUMS (P > 0.05). Conclusion The results suggest that caffeine intake 60 min before 20-km time trials has no effect on the performance or physiological responses of cyclists. PMID:25302056

  14. Single-trial prediction of reaction time variability from MEG brain activity.

    PubMed

    Ohata, Ryu; Ogawa, Kenji; Imamizu, Hiroshi

    2016-06-02

    Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed-reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements.

  15. Single-trial prediction of reaction time variability from MEG brain activity

    PubMed Central

    Ohata, Ryu; Ogawa, Kenji; Imamizu, Hiroshi

    2016-01-01

    Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed-reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements. PMID:27250872

  16. Single-trial prediction of reaction time variability from MEG brain activity.

    PubMed

    Ohata, Ryu; Ogawa, Kenji; Imamizu, Hiroshi

    2016-01-01

    Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed-reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements. PMID:27250872

  17. Single-trial time-frequency analysis of electrocortical signals: baseline correction and beyond.

    PubMed

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

    2014-01-01

    Event-related desynchronization (ERD) and synchronization (ERS) of electrocortical signals (e.g., electroencephalogram [EEG] and magnetoencephalogram) reflect important aspects of sensory, motor, and cognitive cortical processing. The detection of ERD and ERS relies on time-frequency decomposition of single-trial electrocortical signals, to identify significant stimulus-induced changes in power within specific frequency bands. Typically, these changes are quantified by expressing post-stimulus EEG power as a percentage of change relative to pre-stimulus EEG power. However, expressing post-stimulus EEG power relative to pre-stimulus EEG power entails two important and surprisingly neglected issues. First, it can introduce a significant bias in the estimation of ERD/ERS magnitude. Second, it confuses the contribution of pre- and post-stimulus EEG power. Taking the human electrocortical responses elicited by transient nociceptive stimuli as an example, we demonstrate that expressing ERD/ERS as the average percentage of change calculated at single-trial level introduces a positive bias, resulting in an overestimation of ERS and an underestimation of ERD. This bias can be avoided using a single-trial baseline subtraction approach. Furthermore, given that the variability in ERD/ERS is not only dependent on the variability in post-stimulus power but also on the variability in pre-stimulus power, an estimation of the respective contribution of pre- and post-stimulus EEG variability is needed. This can be achieved using a multivariate linear regression (MVLR) model, which could be optimally estimated using partial least square (PLS) regression, to dissect and quantify the relationship between behavioral variables and pre- and post-stimulus EEG activities. In summary, combining single-trial baseline subtraction approach with PLS regression can be used to achieve a correct detection and quantification of ERD/ERS. PMID:24084069

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

    PubMed

    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 < 0.001), and respiratory exchange ratio (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.

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

    PubMed

    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 < 0.001), and respiratory exchange ratio (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. PMID:24978834

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

    PubMed

    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.

  1. Time-dependent changes in excitability after one-trial conditioning of Hermissenda.

    PubMed

    Crow, T; Siddiqi, V

    1997-12-01

    The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. A one-trial conditioning procedure consisting of light paired with the application of serotonin (5-HT) to the exposed, but otherwise intact, nervous system produces suppression of phototactic behavior tested 24 h after conditioning. Short- and long-term enhancement (STE and LTE) of excitability in identified type B photoreceptors is a cellular correlate of one-trial conditioning. LTE can be expressed in the absence of STE suggesting that STE and LTE may be parallel processes. To examine the development of enhancement, we studied its time-dependent alterations after one-trial conditioning. Intracellular recordings from identified type B photoreceptors of independent groups collected at different times after conditioning revealed that enhanced excitability follows a biphasic pattern in its development. The analysis of spikes elicited by 2 and 30 s extrinsic current pulses at different levels of depolarization showed that enhancement reached a peak 3 h after conditioning. From its peak, excitability decreased toward baseline control levels 5-6 h after conditioning followed by an increase to a stable plateau at 16 to 24 h postconditioning. Excitability changes measured in cells from unpaired control groups showed maximal changes 1 h posttreatment that rapidly decremented within 2 h. The conditioned stimulus (CS) elicited significantly more spikes 24 h postconditioning for the conditioned group as compared with the unpaired control group. The analysis of the time-dependent development of enhancement may reveal the processes underlying different stages of memory for this associative experience.

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

    PubMed

    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. PMID:25710190

  3. Operating Room Time Savings with the Use of Splint Packs: A Randomized Controlled Trial

    PubMed Central

    Gonzalez, Tyler A.; Bluman, Eric M.; Palms, David; Smith, Jeremy T.; Chiodo, Christopher P.

    2016-01-01

    Background: The most expensive variable in the operating room (OR) is time. Lean Process Management is being used in the medical field to improve efficiency in the OR. Streamlining individual processes within the OR is crucial to a comprehensive time saving and cost-cutting health care strategy. At our institution, one hour of OR time costs approximately $500, exclusive of supply and personnel costs. Commercially prepared splint packs (SP) contain all components necessary for plaster-of-Paris short-leg splint application and have the potential to decrease splint application time and overall costs by making it a more lean process. We conducted a randomized controlled trial comparing OR time savings between SP use and bulk supply (BS) splint application. Methods: Fifty consecutive adult operative patients on whom post-operative short-leg splint immobilization was indicated were randomized to either a control group using BS or an experimental group using SP. One orthopaedic surgeon (EMB) prepared and applied all of the splints in a standardized fashion. Retrieval time, preparation time, splint application time, and total splinting time for both groups were measured and statistically analyzed. Results: The retrieval time, preparation time and total splinting time were significantly less (p<0.001) in the SP group compared with the BS group. There was no significant difference in application time between the SP group and BS group. Conclusion: The use of SP made the process of splinting more lean. This has resulted in an average of 2 minutes 52 seconds saved in total splinting time compared to BS, making it an effective cost-cutting and time saving technique. For high volume ORs, use of splint packs may contribute to substantial time and cost savings without impacting patient safety. PMID:26894212

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

    PubMed

    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.

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

    PubMed

    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. PMID:22868289

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

    PubMed

    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.

  7. Just-in-Time Information Improved Decision-Making in Primary Care: A Randomized Controlled Trial

    PubMed Central

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

    2008-01-01

    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 decision

  8. Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists.

    PubMed

    Muggeridge, David J; Sculthorpe, Nicholas; Grace, Fergal M; Willis, Gareth; Thornhill, Laurence; Weller, Richard B; James, Philip E; Easton, Chris

    2015-08-01

    Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 ± 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 × 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean ± SD 1447 ± 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 ± 40 s; d = 0.41) or NIT + SHAM (1455 ± 47 s; d = 0.28) compared to PLA + SHAM (1469 ± 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve

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

    PubMed Central

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

    2014-01-01

    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. PMID:24968210

  10. Modeling Population Spike Trains with Specified Time-Varying Spike Rates, Trial-to-Trial Variability, and Pairwise Signal and Noise Correlations.

    PubMed

    Lyamzin, Dmitry R; Macke, Jakob H; Lesica, Nicholas A

    2010-01-01

    As multi-electrode and imaging technology begin to provide us with simultaneous recordings of large neuronal populations, new methods for modeling such data must also be developed. Here, we present a model for the type of data commonly recorded in early sensory pathways: responses to repeated trials of a sensory stimulus in which each neuron has it own time-varying spike rate (as described by its PSTH) and the dependencies between cells are characterized by both signal and noise correlations. This model is an extension of previous attempts to model population spike trains designed to control only the total correlation between cells. In our model, the response of each cell is represented as a binary vector given by the dichotomized sum of a deterministic "signal" that is repeated on each trial and a Gaussian random "noise" that is different on each trial. This model allows the simulation of population spike trains with PSTHs, trial-to-trial variability, and pairwise correlations that match those measured experimentally. Furthermore, the model also allows the noise correlations in the spike trains to be manipulated independently of the signal correlations and single-cell properties. To demonstrate the utility of the model, we use it to simulate and manipulate experimental responses from the mammalian auditory and visual systems. We also present a general form of the model in which both the signal and noise are Gaussian random processes, allowing the mean spike rate, trial-to-trial variability, and pairwise signal and noise correlations to be specified independently. Together, these methods for modeling spike trains comprise a potentially powerful set of tools for both theorists and experimentalists studying population responses in sensory systems.

  11. Biomarker driven population enrichment for adaptive oncology trials with time to event endpoints.

    PubMed

    Mehta, Cyrus; Schäfer, Helmut; Daniel, Hanna; Irle, Sebastian

    2014-11-20

    The development of molecularly targeted therapies for certain types of cancers has led to the consideration of population enrichment designs that explicitly factor in the possibility that the experimental compound might differentially benefit different biomarker subgroups. In such designs, enrollment would initially be open to a broad patient population with the option to restrict future enrollment, following an interim analysis, to only those biomarker subgroups that appeared to be benefiting from the experimental therapy. While this strategy could greatly improve the chances of success for the trial, it poses several statistical and logistical design challenges. Because late-stage oncology trials are typically event driven, one faces a complex trade-off between power, sample size, number of events, and study duration. This trade-off is further compounded by the importance of maintaining statistical independence of the data before and after the interim analysis and of optimizing the timing of the interim analysis. This paper presents statistical methodology that ensures strong control of type 1 error for such population enrichment designs, based on generalizations of the conditional error rate approach. The special difficulties encountered with time-to-event endpoints are addressed by our methods. The crucial role of simulation for guiding the choice of design parameters is emphasized. Although motivated by oncology, the methods are applicable as well to population enrichment designs in other therapeutic areas.

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

    PubMed

    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 < 0.001). The 0° torso angle position significantly affected the metabolic and physiological variables compared to all other investigated positions. At constant submaximal intensities of 60, 70 and 80% PPO, all variables significantly increased with increasing intensity (P < 0.0001) and decreasing torso angle (P < 0.005). This study shows that for trained cyclists there should be a trade-off between the aerodynamic drag and physiological functioning.

  13. Assessing potentially time-dependent treatment effect from clinical trials and observational studies for survival data, with applications to the Women's Health Initiative combined hormone therapy trial

    PubMed Central

    Yang, Song; Prentice, Ross L.

    2015-01-01

    For risk and benefit assessment in clinical trials and observational studies with time-to-event data, the Cox model has usually been the model of choice. When the hazards are possibly non-proportional, a piece-wise Cox model over a partition of the time axis may be considered. Here we propose to analyze clinical trials or observational studies with time-to-event data using a certain semiparametric model. The model allows for a time-dependent treatment effect. It includes the important proportional hazards model as a sub-model, and can accommodate various patterns of time-dependence of the hazard ratio. After estimation of the model parameters using a pseudo-likelihood approach, simultaneous confidence intervals for the hazard ratio function are established using a Monte Carlo method to assess the time-varying pattern of the treatment effect. To assess the overall treatment effect, estimated average hazard ratio and its confidence intervals are also obtained. The proposed methods are applied to data from the Women's Health Initiative. To compare the WHI clinical trial and observational study, we use the propensity score in building the regression model. Compared to the piece-wise Cox model, the proposed model yields a better model fit and does not require partitioning of the time axis. PMID:25689356

  14. Oral contraceptive cycle phase does not affect 200-m swim time trial performance.

    PubMed

    Rechichi, Claire; Dawson, Brian

    2012-04-01

    The purpose of this study was to examine whether swimming performance was affected by acute hormonal fluctuation within a monophasic oral contraceptive (OC) cycle. Six competitive swimmers and water polo players completed a 200-m time trial at 3 time points of a single OC cycle: during the consumption phase (CONS), early (WITH1), and late in the withdrawal phase (WITH2). Split times and stroke rate were recorded during the time trial, and heart rate, blood lactate, glucose, and pH were measured after each performance test. Resting endogenous serum estradiol and progesterone concentrations were also assessed. No significant differences were observed between phases for body composition, 200-m swim time, mean stroke rate, peak heart rate, or blood glucose (p > 0.05). The mean peak blood lactate was significantly lower during WITH2 (9.9 ± 3.0 mmol·L(-1)) compared with that of CONS (12.5 ± 3.0 mmol·L(-1)) and mean pH higher during WITH2 (7.183 ± 0.111) compared with that of CONS (7.144 ± 0.092). Serum estradiol levels were significantly greater during WITH2 compared with that during WITH1 and CONS, but there was no difference in serum progesterone levels. These results demonstrate that for monophasic OC users, cycle phase does not impact the 200-m swimming performance. There was a reduction in blood lactate and an increase in pH during the withdrawal phase, possibly because of an increase in fluid retention, plasma volume, and cellular alkalosis. Therefore, female 200-m swimmers taking a monophasic OC need not be concerned by the phase of their cycle with regard to competition and optimizing performance. However, coaches and scientists should exercise caution when interpreting blood lactate results obtained from swimming tests and consider controlling for cycle phase for athletes taking an OC. PMID:22446669

  15. The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males.

    PubMed

    Logan-Sprenger, Heather M; Heigenhauser, George J F; Jones, Graham L; Spriet, Lawrence L

    2015-08-01

    This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a -0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated.

  16. The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males

    PubMed Central

    Logan-Sprenger, Heather M; Heigenhauser, George JF; Jones, Graham L; Spriet, Lawrence L

    2015-01-01

    This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ∼65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a −0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated. PMID:26296770

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

    PubMed

    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 < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with 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. PMID:25154895

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

    PubMed

    Berkulo, Meriam A R; Bol, Susan; Levels, Koen; Lamberts, Robert P; Daanen, Hein A M; Noakes, Timothy 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 two 40-km cycling TTs hypohydrated. During one hypohydrated trial no fluid was ingested (HYPO), during the other trial ad-libitum water ingestion was allowed (FLUID). Ambient temperature was 35.2 ± 0.2 °C, relative humidity 51 ± 3% and airflow 7 m·s(-1). Body mass (BM) was determined at the start of the test, and before and after the TT. During the TT, power output, heart rate (HR), gastrointestinal temperature, mean skin temperature, rating of perceived exertion (RPE), thermal sensation, thermal comfort and thirst sensation were measured. Prior to the start of the TT, BM was 1.2% lower in HYPO and FLUID compared to EU. During the TT, BM loss in FLUID was lower compared to EU and HYPO (1.0 ± 0.8%, 2.7 ± 0.2% and 2.6 ± 0.3%, respectively). Hydration status had no effect on power output (EU: 223 ± 32 W, HYPO: 217 ± 39 W, FLUID: 224 ± 35 W), HR, gastrointestinal temperature, mean skin temperature, RPE, thermal sensation and thermal comfort. Thirst sensation was higher in HYPO than in EU and FLUID. It was concluded that hypohydration did not adversely affect performance during a 40-km cycling TT in the heat. Therefore, whether or not participants consumed fluid during exercise did not influence their TT performance.

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

    PubMed

    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 < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with 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.

  20. The effect of interruptions during training on the time to the first trial and race start in Thoroughbred racehorses.

    PubMed

    Bolwell, C F; Rogers, C W; French, N P; Firth, E C

    2013-02-01

    Few studies have investigated the effect of having interruptions during training on future training and racing performance in Thoroughbred racehorses. The aim of this paper was to investigate the effect of having an interruption before the first trial on starting in a trial or a race. A prospective cohort study was used to record the training activity of a cohort of Thoroughbred racehorses, over two racing seasons. Fourteen racehorse trainers recorded information on the distances worked at canter and at fast speeds (<15s/200 m) and provided reasons for horses not training, or for having interruptions (break from training). Trial and racing results were obtained from the New Zealand Thoroughbred Racing online database. A Cox proportional hazards regression model was used to investigate two outcome measures of performance: (1) time to the first trial and (2) time to the first race. The type of interruption that had occurred before the first trial was the main exposure of interest, and was grouped into: no interruption, voluntary (no known condition or disease present) and involuntary interruptions (due to the presence of a condition or disease). A total of 160/200 (80%) horses started in at least one trial and 100/205 (48%) horses started in at least one race during the study period. The median time to starting in a trial or a race differed significantly (p<0.001) with the type of interruption. The hazard of starting in a trial was lower for horses experiencing voluntary and involuntary interruptions (p<0.001) but there was no association with starting in a race, after adjusting for confounding variables. As age at the start of training increased the hazard of starting in a trial decreased. Horses accumulating longer distances at 15s/200 m had a higher hazard of starting in a trial, whilst horses accumulating fewer events at high speed and fewer trials had a reduced hazard of starting in a race. There was significant clustering at the trainer level for both the

  1. Comparing the effect of clopidogrel versus ticagrelor on coronary microvascular dysfunction in acute coronary syndrome patients (TIME trial): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Although prompt reperfusion treatment restores normal epicardial flow, microvascular dysfunction may persist in some patients with acute coronary syndrome (ACS). Impaired myocardial perfusion is caused by intraluminal platelets, fibrin thrombi and neutrophil plugging; antiplatelet agents play a significant role in terms of protecting against thrombus microembolization. A novel antiplatelet agent, ticagrelor, is a non-thienopyridine, direct P2Y12 blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the effects of ticagrelor on the prevention of microvascular dysfunction are uncertain. The present study is a comparison between clopidogrel and ticagrelor use for preventing microvascular dysfunction in patients with ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI, respectively). Methods/design The TIME trial is a single-center, randomized, open-label, parallel-arm study designed to demonstrate the superiority of ticagrelor over clopidogrel. A total of 152 patients with a spectrum of STEMI or NSTEMI will undergo prospective random assignment to clopidogrel or ticagrelor (1:1 ratio). The primary endpoint is an index of microcirculatory resistance (IMR) measured after percutaneous coronary intervention (PCI); the secondary endpoint is wall motion score index assessed at 3 months by using echocardiography. Discussion The TIME trial is the first study designed to compare the protective effect of clopidogrel and ticagrelor on coronary microvascular dysfunction in patients with STEMI and NSTEMI. Trial registration ClinicalTrials.gov: NCT02026219. Registration date: 24 December 2013. PMID:24885437

  2. Time-related trends in variability of cIMT changes in statin trials.

    PubMed

    Davidson, Michael H; Tomassini, Joanne E; Jensen, Erin; Neff, David; Polis, Adam B; Tershakovec, Andrew M

    2016-03-01

    This brief article provides complementary data supporting the results reported in "Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006" [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988-2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of lipid

  3. Time-related trends in variability of cIMT changes in statin trials

    PubMed Central

    Davidson, Michael H.; Tomassini, Joanne E.; Jensen, Erin; Neff, David; Polis, Adam B.; Tershakovec, Andrew M.

    2015-01-01

    This brief article provides complementary data supporting the results reported in “Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006” [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988–2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of

  4. Augmented case-only designs for randomized clinical trials with failure time endpoints

    PubMed Central

    2015-01-01

    Summary Under suitable assumptions and by exploiting the independence between inherited genetic susceptibility and treatment assignment, the case-only design yields efficient estimates for subgroup treatment effects and gene-treatment interaction in a Cox model. However it cannot provide estimates of the genetic main effect and baseline hazards, that are necessary to compute the absolute disease risk. For two-arm, placebo-controlled trials with rare failure time endpoints, we consider augmenting the case-only design with random samples of controls from both arms, as in the classical case-cohort sampling scheme, or with a random sample of controls from the active treatment arm only. The latter design is motivated by vaccine trials for cost-effective use of resources and specimens so that host genetics and vaccine-induced immune responses can be studied simultaneously in a bigger set of participants. We show that these designs can identify all parameters in a Cox model and that the efficient case-only estimator can be incorporated in a two-step plug-in procedure. Results in simulations and a data example suggest that incorporating case-only estimators in the classical case-cohort design improves the precision of all estimated parameters; sampling controls only in the active treatment arm attains a similar level of efficiency. PMID:26347982

  5. Effects of Tai Chi on the protracted abstinence syndrome: a time trial analysis.

    PubMed

    Li, De-Xiang; Zhuang, Xin-Ying; Zhang, Yi-Ping; Guo, Hao; Wang, Ze; Zhang, Qing; Feng, Yue-Mei; Yao, Yong-Gang

    2013-01-01

    While exercise has been shown to reduce the negative effects of substance withdrawal symptoms, no research has investigated if Tai Chi, a traditional Chinese exercise, has similar effects. Here, we observed the physiological effects of Tai Chi on protracted abstinence syndrome (PAS) in female heroin addicts by comprehensively inspecting their immune system function, complete blood count, hepatic function and renal function. To determine the psychological effects, we used the Hamilton Rating Scale for Depression (HRSD) and the rating scale of heroin withdrawal symptoms. We recruited 70 heroin-addicted young women beginning to undergo withdrawal and randomly assigned them into two groups: one group received one-hour Tai Chi exercise every two days (Tai Chi group, n = 36) and the other group did not (control group, n = 34). Thirty-three patients finished this six-month trial. Numerous significant physiological differences were observed between all heroin-addicted subjects (n = 70) and age-matched healthy individuals (n = 18), suggesting a deleterious effect of drug addiction. There were improvements for certain physical parameters between the Tai Chi group (n = 17) and the control group (n = 16), although the differences were not statistically significant. We observed a small significant difference in psychological effects near the 60-day mark between the two groups. Taken together, our results suggest that Tai Chi might have a positive effect on PAS, which future studies can confirm by using an expanded sample size, longer trial time, and more sensitive and specific indicators of psychological and physiological health.

  6. Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

    PubMed

    Geffen, N; Aagaard, P; Corbelli, G M; Meulbroek, M; Peavy, D; Rappoport, C; Schwarze, S; Collins, S

    2015-04-01

    Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500 cells/μL, while the threshold for the UK and South Africa remains at 350 cells/μL. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500 cells/μL or higher versus deferring treatment until the CD4 cell count decreases to 350 cells/μL or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people.

  7. Timing and selection for renal revascularization in an era of negative trials: what to do?

    PubMed

    Textor, Stephen C; McKusick, Michael M; Misra, Sanjay; Glockner, James

    2009-01-01

    Management of atherosclerotic renal artery stenosis has become more complex with advances in both medical therapy and endovascular procedures. Results from recent trials fail to demonstrate major benefits of endovascular stenting in addition to optimal medical therapy. The general applicability of these results to many patients is limited by short-term follow-up and selection biases in recruitment. Many patients at highest risk were excluded from these studies and some were included with trivial lesions. Identification of patients with hemodynamically significant lesions remains a challenge and has led to more stringent criteria for Doppler ultrasound, measurement of translesional gradients and quantitative angiography. Although many patients can now be managed with medical therapy, it should be recognized that long-term reduction in antihypertensive drug requirements and recovery of kidney function are limited to those undergoing renal revascularization. As with any major vascular lesion, follow-up for disease stability and/or progression is essential. The ambiguity of present trial data may lead some to overlook selected subgroups that would benefit from restoring renal blood supply through revascularization. Further studies to more precisely identify kidneys that can recover function and/or are beyond meaningful recovery are essential. Considering the comorbid risks for the atherosclerotic population, it will remain imperative for clinicians to consider the hazards, costs and benefits carefully for each patient to determine the role and timing for both medical therapy and revascularization.

  8. Augmented case-only designs for randomized clinical trials with failure time endpoints.

    PubMed

    Dai, James Y; Zhang, Xinyi Cindy; Wang, Ching-Yun; Kooperberg, Charles

    2016-03-01

    Under suitable assumptions and by exploiting the independence between inherited genetic susceptibility and treatment assignment, the case-only design yields efficient estimates for subgroup treatment effects and gene-treatment interaction in a Cox model. However it cannot provide estimates of the genetic main effect and baseline hazards, that are necessary to compute the absolute disease risk. For two-arm, placebo-controlled trials with rare failure time endpoints, we consider augmenting the case-only design with random samples of controls from both arms, as in the classical case-cohort sampling scheme, or with a random sample of controls from the active treatment arm only. The latter design is motivated by vaccine trials for cost-effective use of resources and specimens so that host genetics and vaccine-induced immune responses can be studied simultaneously in a bigger set of participants. We show that these designs can identify all parameters in a Cox model and that the efficient case-only estimator can be incorporated in a two-step plug-in procedure. Results in simulations and a data example suggest that incorporating case-only estimators in the classical case-cohort design improves the precision of all estimated parameters; sampling controls only in the active treatment arm attains a similar level of efficiency.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26997924

  10. Aerodynamics of a cycling team in a time trial: does the cyclist at the front benefit?

    NASA Astrophysics Data System (ADS)

    Íñiguez-de-la Torre, A.; Íñiguez, J.

    2009-11-01

    When seasonal journeys take place in nature, birds and fishes migrate in groups. This provides them not only with security but also a considerable saving of energy. The power they need to travel requires overcoming aerodynamic or hydrodynamic drag forces, which can be substantially reduced when the group travels in an optimal arrangement. Also in this area, humans imitate nature, which is especially evident in the practice of outdoor sports and motor competitions. Cycle races, in which speeds of up to 15 m s-1 are frequent, offer great opportunities to appreciate the advantage of travelling in a group. Here we present a brief analysis of the aerodynamics of a cycling team in a time-trial challenge, showing how each rider is favoured according to his position in the group. We conclude that the artificial tail wind created by the team also benefits the cyclist at the front by about 5%.

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

    PubMed Central

    Rosenbloom, Daniel I. S.; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R.

    2016-01-01

    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 residual reservoir

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

    PubMed

    Hill, Alison L; Rosenbloom, Daniel I S; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R; Siliciano, Robert F; Henrich, Timothy J

    2016-04-01

    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 residual reservoir that

  13. Chemical composition of tropospheric air masses encountered during high altitude flights (>11.5 km) during the 2009 fall Operation Ice Bridge field campaign

    NASA Astrophysics Data System (ADS)

    Yang, Mei Ying Melissa; Vay, Stephanie A.; Stohl, Andreas; Choi, Yonghoon; Diskin, Glenn S.; Sachse, Glen W.; Blake, Donald R.

    2012-09-01

    As part of the 2009 Operation Ice Bridge campaign, the NASA DC-8 aircraft was used to fill the data-time gap in laser observation of the changes in ice sheets, glaciers and sea ice between ICESat-I (Ice, Cloud, and land Elevation Satellite) and ICESat-II. Complementing the cryospheric instrument payload were four in situ atmospheric sampling instruments integrated onboard to measure trace gas concentrations of CO2, CO, N2O, CH4, water vapor and various VOCs (Volatile Organic Compounds). This paper examines two plumes encountered at high altitude (12 km) during the campaign; one during a southbound transit flight (13°S) and the other at 86°S over Antarctica. The data presented are especially significant as the Southern Hemisphere is heavily under-sampled during the austral spring, with few if any high-resolution airborne observations of atmospheric gases made over Antarctica. Strong enhancements of CO, CH4, N2O, CHCl3, OCS, C2H6, C2H2 and C3H8 were observed in the two intercepted air masses that exhibited variations in VOC composition suggesting different sources. The transport model FLEXPART showed that the 13°S plume contained predominately biomass burning emissions originating from Southeast Asia and South Africa, while both anthropogenic and biomass burning emissions were observed at 86°S with South America and South Africa as indicated source regions. The data presented here show evidence that boundary layer pollution is transported from lower latitudes toward the upper troposphere above the South Pole, which may not have been observed in the past.

  14. Airborne characterization of subsaturated aerosol hygroscopicity and dry refractive index from the surface to 6.5 km during the SEAC4RS campaign

    NASA Astrophysics Data System (ADS)

    Shingler, Taylor; Crosbie, Ewan; Ortega, Amber; Shiraiwa, Manabu; Zuend, Andreas; Beyersdorf, Andreas; Ziemba, Luke; Anderson, Bruce; Thornhill, Lee; Perring, Anne E.; Schwarz, Joshua P.; Campazano-Jost, Pedro; Day, Douglas A.; Jimenez, Jose L.; Hair, Johnathan W.; Mikoviny, Tomas; Wisthaler, Armin; Sorooshian, Armin

    2016-04-01

    In situ aerosol particle measurements were conducted during 21 NASA DC-8 flights in the Studies of Emissions and Atmospheric Composition, Clouds, and Climate Coupling by Regional Surveys field campaign over the United States, Canada, Pacific Ocean, and Gulf of Mexico. For the first time, this study reports rapid, size-resolved hygroscopic growth and real refractive index (RI at 532 nm) data between the surface and upper troposphere in a variety of air masses including wildfires, agricultural fires, biogenic, marine, and urban outflow. The Differential Aerosol Sizing and Hygroscopicity Spectrometer Probe (DASH-SP) quantified size-resolved diameter growth factors (GF = Dp,wet/Dp,dry) that are used to infer the hygroscopicity parameter κ. Thermokinetic simulations were conducted to estimate the impact of partial particle volatilization within the DASH-SP across a range of sampling conditions. Analyses of GF and RI data as a function of air mass origin, dry size, and altitude are reported, in addition to κ values for the inorganic and organic fractions of aerosol. Average RI values are found to be fairly constant (1.52-1.54) for all air mass categories. An algorithm is used to compare size-resolved DASH-SP GF with bulk scattering f(RH = 80%) data obtained from a pair of nephelometers, and the results show that the two can only be reconciled if GF is assumed to decrease with increasing dry size above 400 nm (i.e., beyond the upper bound of DASH-SP measurements). Individual case studies illustrate variations of hygroscopicity as a function of dry size, environmental conditions, altitude, and composition.

  15. Microbial Sulfate Reduction Potential in Coal-Bearing Sediments Down to ~2.5 km below the Seafloor off Shimokita Peninsula, Japan

    PubMed Central

    Glombitza, Clemens; Adhikari, Rishi R.; Riedinger, Natascha; Gilhooly, William P.; Hinrichs, Kai-Uwe; Inagaki, Fumio

    2016-01-01

    Sulfate reduction is the predominant anaerobic microbial process of organic matter mineralization in marine sediments, with recent studies revealing that sulfate reduction not only occurs in sulfate-rich sediments, but even extends to deeper, methanogenic sediments at very low background concentrations of sulfate. Using samples retrieved off the Shimokita Peninsula, Japan, during the Integrated Ocean Drilling Program (IODP) Expedition 337, we measured potential sulfate reduction rates by slurry incubations with 35S-labeled sulfate in deep methanogenic sediments between 1276.75 and 2456.75 meters below the seafloor. Potential sulfate reduction rates were generally extremely low (mostly below 0.1 pmol cm−3 d−1) but showed elevated values (up to 1.8 pmol cm−3 d−1) in a coal-bearing interval (Unit III). A measured increase in hydrogenase activity in the coal-bearing horizons coincided with this local increase in potential sulfate reduction rates. This paired enzymatic response suggests that hydrogen is a potentially important electron donor for sulfate reduction in the deep coalbed biosphere. By contrast, no stimulation of sulfate reduction rates was observed in treatments where methane was added as an electron donor. In the deep coalbeds, small amounts of sulfate might be provided by a cryptic sulfur cycle. The isotopically very heavy pyrites (δ34S = +43‰) found in this horizon is consistent with its formation via microbial sulfate reduction that has been continuously utilizing a small, increasingly 34S-enriched sulfate reservoir over geologic time scales. Although our results do not represent in-situ activity, and the sulfate reducers might only have persisted in a dormant, spore-like state, our findings show that organisms capable of sulfate reduction have survived in deep methanogenic sediments over more than 20 Ma. This highlights the ability of sulfate-reducers to persist over geological timespans even in sulfate-depleted environments. Our study

  16. Long Term Borehole Monitoring System For NanTroSEIZE 3.5 km Riser Hole: Environmental Life Test and Land Test

    NASA Astrophysics Data System (ADS)

    Kyo, M.; Araki, E.; Ito, H.

    2009-12-01

    Most of the large earthquakes (magnitude greater than 8.0) observed in Japan fall into the subduction plate-boundary category. Based on the results of previous Nankai Trough research efforts, further research opportunities have been proposed under the umbrella of the IODP scientific drilling proposal 603 (NanTroSEIZE: Nankai Trough Seismogenic Zone Experiment) ranked as the top level proposal in IODP. IODP proposal 603 not only proposes drilling, coring and geological analysis, and geophysical logging, but also mandates that a long-term borehole monitoring system be installed into two deep riser holes at about 3,500 m and about 6,000 m below sea floor (mbsf), where we expect to encounter the mega-splay and the locked region of mega thrust fault, respectively. The target of 3,500 m riser hole is expected to drill through five potential splay faults above 3,500 mbsf. We plan to install sensors to monitor strain, tilt and optionally pore pressure for crustal deformation at and between splay faults, to monitor seismometer array for micro and slow earthquakes detection and for seismic microstructures, and to monitor pore pressure and temperature for hydrologic state change at the fault during interseismic period. The major technical features to develop the borehole observatory for 3,500 m riser hole are mainly as follows; 1) high temperature (125°C), 2) long life (5 years), 3) deployment (15,000 psi wellhead system, deep well, retrieval, perforation, packer, mechanical shock), 4) coupling to formation (cement, clamp), 5) multi level monitoring (against 5 spray faults), 6) multi purpose monitoring (seismic, geodetic, hydrogeologic), 7) low power consumption, 8) real time monitoring (connecting to sea bed cable), 9) accurate synchronization, 10) wide frequency range / high dynamic range ADC, 11) down sizing (installing into 9-5/8”casing with tubing), 12) system redundancy (fault tolerant). We started the development of an experimental prototype (EXP) for field test

  17. Long Term Borehole Monitoring System For NanTroSEIZE 3.5 km Riser Hole: Component Level Life Test of Telemetry System.

    NASA Astrophysics Data System (ADS)

    Kyo, M.; Ito, H.; Namba, Y.; Kato, K.; Koseki, K.; Kuramoto, S.; Araki, E.

    2008-12-01

    Most of the large earthquakes (magnitude greater than 8.0) observed in Japan fall into the subduction plate- boundary category. Based on the results of previous Nankai Trough research efforts, further research opportunities have been proposed under the umbrella of the IODP scientific drilling proposal 603 (NanTroSEIZE: Nankai Trough Seismogenic Zone Experiment) ranked as the top level proposal in IODP. IODP proposal 603 not only proposes drilling, coring and geological analysis, and geophysical logging, but also mandates that a long-term borehole monitoring system be installed into two deep riser holes at about 3,500 m and about 6,000 m below sea floor (mbsf), where we expect to encounter the mega-splay and the locked region of mega thrust fault, respectively. The target of 3,500 m riser hole is expected to drill through five potential splay faults above 3,500 mbsf. We plan to install sensors to monitor strain, tilt and optionally pore pressure for crustal deformation at and between splay faults, to monitor seismometer array for micro and slow earthquakes detection and for seismic microstructures, and to monitor pore pressure and temperature for hydrologic state change at the fault during interseismic period. The major technical features to develop the borehole observatory for 3,500 m riser hole are mainly as follows; 1) high temperature (125C), 2) long life (5 years), 3) deployment (15,000 psi wellhead system, deep well, retrieval, perforation, packer, mechanical shock), 4) coupling to formation (cement, clamp), 5) multi level monitoring (against 5 spray faults), 6) multi purpose monitoring (seismic, geodetic, hydrogeologic), 7) low power consumption, 8) real time monitoring (connecting to sea bed cable), 9) accurate synchronization, 10) wide frequency range / high dynamic range ADC, 11) down sizing (installing into 9-5/8"hcasing with tubing), 12) system redundancy (fault tolerant). We started the development of an experimental prototype (EXP) for field test using

  18. Time-dependent approach for single trial classification of covert visuospatial attention

    NASA Astrophysics Data System (ADS)

    Tonin, L.; Leeb, R.; Millán, J. del R.

    2012-08-01

    Recently, several studies have started to explore covert visuospatial attention as a control signal for brain-computer interfaces (BCIs). Covert visuospatial attention represents the ability to change the focus of attention from one point in the space without overt eye movements. Nevertheless, the full potential and possible applications of this paradigm remain relatively unexplored. Voluntary covert visuospatial attention might allow a more natural and intuitive interaction with real environments as neither stimulation nor gazing is required. In order to identify brain correlates of covert visuospatial attention, classical approaches usually rely on the whole α-band over long time intervals. In this work, we propose a more detailed analysis in the frequency and time domains to enhance classification performance. In particular, we investigate the contribution of α sub-bands and the role of time intervals in carrying information about visual attention. Previous neurophysiological studies have already highlighted the role of temporal dynamics in attention mechanisms. However, these important aspects are not yet exploited in BCI. In this work, we studied different methods that explicitly cope with the natural brain dynamics during visuospatial attention tasks in order to enhance BCI robustness and classification performances. Results with ten healthy subjects demonstrate that our approach identifies spectro-temporal patterns that outperform the state-of-the-art classification method. On average, our time-dependent classification reaches 0.74 ± 0.03 of the area under the ROC (receiver operating characteristic) curve (AUC) value with an increase of 12.3% with respect to standard methods (0.65 ± 0.4). In addition, the proposed approach allows faster classification (<1 instead of 3 s), without compromising performances. Finally, our analysis highlights the fact that discriminant patterns are not stable for the whole trial period but are changing over short time

  19. The effects of different doses of caffeine on endurance cycling time trial performance.

    PubMed

    Desbrow, Ben; Biddulph, Caren; Devlin, Brooke; Grant, Gary D; Anoopkumar-Dukie, Shailendra; Leveritt, Michael D

    2012-01-01

    This study investigated the effects of two different doses of caffeine on endurance cycle time trial performance in male athletes. Using a randomised, placebo-controlled, double-blind crossover study design, sixteen well-trained and familiarised male cyclists (Mean ± s: Age = 32.6 ± 8.3 years; Body mass = 78.5 ± 6.0 kg; Height = 180.9 ± 5.5 cm VO2(peak) = 60.4 ± 4.1 ml x kg(-1) x min(-1)) completed three experimental trials, following training and dietary standardisation. Participants ingested either a placebo, or 3 or 6 mg x kg(-1) body mass of caffeine 90 min prior to completing a set amount of work equivalent to 75% of peak sustainable power output for 60 min. Exercise performance was significantly (P < 0.05) improved with both caffeine treatments as compared to placebo (4.2% with 3 mg x kg(-1) body mass and 2.9% with 6 mg x kg(-1) body mass). The difference between the two caffeine doses was not statistically significant (P = 0.24). Caffeine ingestion at either dose resulted in significantly higher heart rate values than the placebo conditions (P < 0.05), but no statistically significant treatment effects in ratings of perceived exertion (RPE) were observed (P = 0.39). A caffeine dose of 3 mg x kg(-1) body mass appears to improve cycling performance in well-trained and familiarised athletes. Doubling the dose to 6 mg x kg(-1) body mass does not confer any additional improvements in performance.

  20. Cause, timing, and location of death in the Single Ventricle Reconstruction trial

    PubMed Central

    Ohye, Richard G.; Schonbeck, Julie V.; Eghtesady, Pirooz; Laussen, Peter C.; Pizarro, Christian; Shrader, Peter; Frank, Deborah U.; Graham, Eric M.; Hill, Kevin D.; Jacobs, Jeffrey P.; Kanter, Kirk R.; Kirsh, Joel A.; Lambert, Linda M.; Lewis, Alan B.; Ravishankar, Chitra; Tweddell, James S.; Williams, Ismee A.; Pearson, Gail D.

    2012-01-01

    Objectives The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths. Methods There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event. Results The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome. Conclusions In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate. (J Thorac Cardiovasc Surg 2012;144:907-14) PMID:22901498

  1. Pacing strategy in simulated cycle time-trials is based on perceived rather than actual distance.

    PubMed

    Nikolopoulos, V; Arkinstall, M J; Hawley, J A

    2001-06-01

    This study determined the pacing strategies and performance responses of six well-trained cyclists/triathletes (peak O2 uptake 66.4+/-3.7 ml x kg(-1) x min(-1), mean+/-SD) during seven simulated time-trials (TT) conducted on a wind-braked cycle ergometer. All subjects first performed a 40 km familiarisation ride (TT1). They were then informed they would be riding a further four 40 km TT for the purpose of a reliability study. Instead, the actual distances ridden for the next three TT were a random order of 34 (TT2), 40 (TT3) and 46 km (TT4). The only feedback given to subjects during TT1-4 was the percentage distance of that ride remaining. During a further 40 km TT (TT5) subjects were allowed to view their heart rate (HR) responses throughout the ride. Despite the significantly different performance times across the three distances (47:23+/-4:23 vs 55:57+/-3:24 vs 65:41+/-3:56 min for the 34, 40 and 46 km respectively, P<0.001), average power output (296+/-48 vs 294+/-48 vs 286+/-40 W) and HR (173+/-11 vs 174+/-12 vs 173+/-12 beats x min(-1)) were similar. The true nature of the first part of the study was then revealed to subjects who subsequently completed an additional 34 km and 46 km TT TT6-7) in which the actual and perceived distance ridden was the same. Power output and HR responses were similar for both unknown (TT2 and TT6) and known (TT4 and TT7) rides for both distances: 296+/-48 vs 300+/-55 W and 173+/-11 vs 177+/-11 beats x min(-1) (34 km) and 286+/-40 vs 273+/-42 W and 173+/-12 vs 174+/-12 beats x min(-1) (46 km). In conclusion, well-trained cyclists rode at similar power outputs and HR during time trials they perceived to be the same distance, but which varied in actual distance from 34 to 46 km.

  2. Caffeine Alters Anaerobic Distribution and Pacing during a 4000-m Cycling Time Trial

    PubMed Central

    Santos, Ralmony de Alcantara; Kiss, Maria Augusta Peduti Dal Molin; Silva-Cavalcante, Marcos David; Correia-Oliveira, Carlos Rafaell; Bertuzzi, Romulo; Bishop, David John; Lima-Silva, Adriano Eduardo

    2013-01-01

    The purpose of the present study was to investigate the effects of caffeine ingestion on pacing strategy and energy expenditure during a 4000-m cycling time-trial (TT). Eight recreationally-trained male cyclists volunteered and performed a maximal incremental test and a familiarization test on their first and second visits, respectively. On the third and fourth visits, the participants performed a 4000-m cycling TT after ingesting capsules containing either caffeine (5 mg.kg−1 of body weight, CAF) or cellulose (PLA). The tests were applied in a double-blind, randomized, repeated-measures, cross-over design. When compared to PLA, CAF ingestion increased mean power output [219.1±18.6 vs. 232.8±21.4 W; effect size (ES)  = 0.60 (95% CI = 0.05 to 1.16), p = 0.034] and reduced the total time [419±13 vs. 409±12 s; ES = −0.71 (95% CI = −0.09 to −1.13), p = 0.026]. Furthermore, anaerobic contribution during the 2200-, 2400-, and 2600-m intervals was significantly greater in CAF than in PLA (p<0.05). However, the mean anaerobic [64.9±20.1 vs. 57.3±17.5 W] and aerobic [167.9±4.3 vs. 161.8±11.2 W] contributions were similar between conditions (p>0.05). Similarly, there were no significant differences between CAF and PLA for anaerobic work (26363±7361 vs. 23888±6795 J), aerobic work (68709±2118 vs. 67739±3912 J), or total work (95245±8593 vs. 91789±7709 J), respectively. There was no difference for integrated electromyography, blood lactate concentration, heart rate, and ratings of perceived exertion between the conditions. These results suggest that caffeine increases the anaerobic contribution in the middle of the time trial, resulting in enhanced overall performance. PMID:24058684

  3. Caffeine alters anaerobic distribution and pacing during a 4000-m cycling time trial.

    PubMed

    Santos, Ralmony de Alcantara; Kiss, Maria Augusta Peduti Dal Molin; Silva-Cavalcante, Marcos David; Correia-Oliveira, Carlos Rafaell; Bertuzzi, Romulo; Bishop, David John; Lima-Silva, Adriano Eduardo

    2013-01-01

    The purpose of the present study was to investigate the effects of caffeine ingestion on pacing strategy and energy expenditure during a 4000-m cycling time-trial (TT). Eight recreationally-trained male cyclists volunteered and performed a maximal incremental test and a familiarization test on their first and second visits, respectively. On the third and fourth visits, the participants performed a 4000-m cycling TT after ingesting capsules containing either caffeine (5 mg.kg(-1) of body weight, CAF) or cellulose (PLA). The tests were applied in a double-blind, randomized, repeated-measures, cross-over design. When compared to PLA, CAF ingestion increased mean power output [219.1±18.6 vs. 232.8±21.4 W; effect size (ES)  = 0.60 (95% CI = 0.05 to 1.16), p = 0.034] and reduced the total time [419±13 vs. 409±12 s; ES = -0.71 (95% CI = -0.09 to -1.13), p = 0.026]. Furthermore, anaerobic contribution during the 2200-, 2400-, and 2600-m intervals was significantly greater in CAF than in PLA (p<0.05). However, the mean anaerobic [64.9±20.1 vs. 57.3±17.5 W] and aerobic [167.9±4.3 vs. 161.8±11.2 W] contributions were similar between conditions (p>0.05). Similarly, there were no significant differences between CAF and PLA for anaerobic work (26363±7361 vs. 23888±6795 J), aerobic work (68709±2118 vs. 67739±3912 J), or total work (95245±8593 vs. 91789±7709 J), respectively. There was no difference for integrated electromyography, blood lactate concentration, heart rate, and ratings of perceived exertion between the conditions. These results suggest that caffeine increases the anaerobic contribution in the middle of the time trial, resulting in enhanced overall performance.

  4. Aerodynamics of cyclist posture, bicycle and helmet characteristics in time trial stage.

    PubMed

    Chabroux, Vincent; Barelle, Caroline; Favier, Daniel

    2012-07-01

    The present work is focused on the aerodynamic study of different parameters, including both the posture of a cyclist's upper limbs and the saddle position, in time trial (TT) stages. The aerodynamic influence of a TT helmet large visor is also quantified as a function of the helmet inclination. Experiments conducted in a wind tunnel on nine professional cyclists provided drag force and frontal area measurements to determine the drag force coefficient. Data statistical analysis clearly shows that the hands positioning on shifters and the elbows joined together are significantly reducing the cyclist drag force. Concerning the saddle position, the drag force is shown to be significantly increased (about 3%) when the saddle is raised. The usual helmet inclination appears to be the inclination value minimizing the drag force. Moreover, the addition of a large visor on the helmet is shown to provide a drag coefficient reduction as a function of the helmet inclination. Present results indicate that variations in the TT cyclist posture, the saddle position and the helmet visor can produce a significant gain in time (up to 2.2%) during stages.

  5. Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers.

    PubMed

    Hammann, Felix; Kummer, Oliver; Guercioni, Stefania; Imanidis, Georgios; Drewe, Juergen

    2016-06-28

    Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers. The device was affixed to the ventral side of the leading lower arm of the subjects and was programmed to deliver two pulses of drug within 16h with three delivery rates in a consecutive dose escalation study. Tolerability of the three increasing doses of nicotine was established. Plasma concentration of nicotine exhibited two peaks and one trough and reached therapeutically effective levels that behaved linearly with the drug load concentration of the device. In vivo input rate, delivered amount and elimination kinetics were deduced by pharmacokinetic modeling to analyze device performance. Timing, dose and duration of delivery were controlled by system operation parameters. Hence, feasibility of controlled pulsatile delivery of nicotine at predetermined intervals was demonstrated. After additional optimization, preprogrammed or on demand administration to meet individualized and circadian replacement needs should improve smoking cessation efficacy. PMID:27090163

  6. Acute prior heavy strength exercise bouts improve the 20-km cycling time trial performance.

    PubMed

    Silva, Renato A S; Silva-Júnior, Fernando L; Pinheiro, Fabiano A; Souza, Patrícia F M; Boullosa, Daniel A; Pires, Flávio O

    2014-09-01

    This study verified if a prior 5 repetition maximum (5RM) strength exercise would improve the cycling performance during a 20-km cycling time trial (TT20km). After determination of the 5RM leg press exercise load, 11 trained cyclists performed a TT20km in a control condition and 10-minute after 4 sets of 5RM strength exercise bouts (potentiation condition). Oxygen uptake, blood lactate concentration, ratings of perceived exertion (RPE), and power output data were recorded during the TT20km. Cycling economy index was assessed before the TT20km, and pacing strategy was analyzed assuming a "J-shaped" power output distribution profile. Results were a 6.1% reduction (p ≤ 0.05) in the time to complete the TT20km, a greater cycling economy (p < 0.01), and power output in the first 10% of the TT20km (i.e., trend; p = 0.06) in the potentiation condition. However, no differences were observed in pacing strategy, physiological parameters, and RPE between the conditions. These results suggest that 5RM strength exercise bouts improve the performance in a subsequent TT20km.

  7. The effect of β-alanine supplementation on cycling time trials of different length.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-10-01

    The varying results reported in response to β-alanine supplementation may be related to the duration and nature of the exercise protocol employed. We investigated the effects of β-alanine supplementation on a wide range of cycling performance tests in order to produce a clear concise set of criteria for its efficacy. Fourteen trained cyclists (Age = 24.8 ± 6.7 years; VO2max = 65.4 ± 10.2 mL·kg·min(-1)) participated in this placebo-controlled, double-blind study. Prior to supplementation, subjects completed two (familiarization and baseline) supramaximal cycling bouts until exhaustion (120% pre-supplementation VO2max) and two 1-, 4- and 10-km cycling time trial (TT). Subjects then supplemented orally for 4 weeks with 6.4 g/d placebo or β-alanine and repeated the battery of performance tests. Blood lactate was measured pre-exercise, post-exercise and 5  min post-exercise. β-alanine supplementation elicited significant increases in time to exhaustion (TTE) (17.6 ± 11.5 s; p = 0.013, effect compared with placebo) and was likely to be beneficial to 4-km TT performance time (-7.8 ± 8.1 s; 94% likelihood), despite not being statistically different (p = 0.060). Performance times in the 1- and 10-km TT were not affected by treatment. For the highly trained cyclists in the current study, β-alanine supplementation significantly extended supramaximal cycling TTE and may have provided a worthwhile improvement to 4-km TT performance. However, 1- and 10-km cycling TT performance appears to be unaffected by β-alanine supplementation.

  8. Covariate Adjustment Strategy Increases Power in the Randomized Controlled Trial With Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Safarkhani, Maryam; Moerbeek, Mirjam

    2013-01-01

    In a randomized controlled trial, a decision needs to be made about the total number of subjects for adequate statistical power. One way to increase the power of a trial is by including a predictive covariate in the model. In this article, the effects of various covariate adjustment strategies on increasing the power is studied for discrete-time…

  9. Time-Based Physical Activity Interventions for Weight Loss: A Randomized Trial

    PubMed Central

    Jakicic, John M.; Rickman, Amy D.; Lang, Wei; Davis, Kelliann K.; Gibbs, Bethany Barone; Neiberg, Rebecca; Marcus, Marsha D.

    2014-01-01

    Purpose To examine whether enhancing standard behavior weight loss interventions (SBWP) with additional strategies at the initiation of the intervention (ADOPT) or providing the additional strategies at predetermined times over the intervention period (MAINTAIN) enhances 18 month weight loss. Methods This was a clinical trial with participants (n=195; age= 43.2±8.6 yrs; BMI= 33.0±3.4 kg/m2) randomized to SBWP, ADOPT, or MAINTAIN. All were prescribed an energy restricted diet and physical activity, with group intervention sessions delivered over 18 months. ADOPT received additional phone contact (months 1–3), supervised exercise (months 1–6), and behavior campaigns (months 4–9). MAINTAIN received additional phone contact (months 4–6), supervised exercise (months 7–12), and behavior campaigns (months 13–18). Results There was a significant Group X Time interaction for weight loss (p=0.0032). SBWP lost 9.3±0.9, 7.8±1.1, and 5.9±1.2 kg at 6, 12, and 18 months, respectively. ADOPT lost 8.9±0.9, 7.6±1.2, and 5.8±1.2 kg, and MAINTAIN lost 9.7±0.9, 11.0±1.2, and 9.0±1.2 kg at 6, 12, and 18 months, respectively. The Group X Time interaction for SBWP vs. MAINTAIN (p=0.0033) and ADOPT vs. MAINTAIN (p=0.0075) was significant. There was a significant Group X Time interaction for change in fitness (p=0.0060). The Group X Time interaction for MAINTAIN vs. ADOPT (p=0.0018) was significant with a trend for MAINTAIN vs. SBWP (p=0.0525). Conclusions MAINTAIN improved 18-month weight loss compared to SBWP and ADOPT, with statistical trends that MAINTAIN resulted in greater improvements in fitness. These results suggest that time-based strategies emphasizing physical activity conferred greater benefits when delivered later and over the full course of intervention. This provides valuable information for the implementation of time-based strategies to improve long-term weight loss and fitness in overweight and obese adults. PMID:25160843

  10. Strategies of dietary carbohydrate manipulation and their effects on performance in cycling time trials.

    PubMed

    Correia-Oliveira, Carlos Rafaell; Bertuzzi, Romulo; Dal'Molin Kiss, Maria Augusta Peduti; Lima-Silva, Adriano Eduardo

    2013-08-01

    The relationship between carbohydrate (CHO) availability and exercise performance has been thoroughly discussed. CHO improves performance in both prolonged, low-intensity and short, high-intensity exercises. Most studies have focused on the effects of CHO supplementation on the performance of constant-load, time-to-exhaustion exercises. Nevertheless, in the last 20 years, there has been a consistent increase in research on the effects of different forms of CHO supplementation (e.g., diet manipulation, CHO supplementation before or during exercise) on performance during closed-loop exercises, such as cycling time trials (TTs). A TT is a highly reproducible exercise and reflects a more realistic scenario of competition compared with the time-to-exhaustion test. CHO manipulation has been performed in various time periods, such as days before, minutes before, during a TT or in a matched manner (e.g. before and during a TT). The purpose of this review is to address the possible effects of these different forms of CHO manipulation on the performance during a cycling TT. Previous data suggest that when a high-CHO diet (~70% of CHO) is consumed before a TT (24-72 h before), the mean power output increases and reduces the TT time. When participants are supplemented with CHO (from 45 to 400 g) prior to a TT (from 2 min to 6 h before the TT), mean power output and time seem to improve due to an increase in CHO oxidation. Similarly, this performance also seems to increase when participants ingest CHO during a TT because such consumption maintains plasma glucose levels. A CHO mouth rinse also improves performance by activating several brain areas related to reward and motor control through CHO receptors in the oral cavity. However, some studies reported controversial results concerning the benefits of CHO on TT performance. Methodological issues such as time of supplementation, quantity, concentration and type of CHO ingested, as well as the TT duration and intensity, should be

  11. Effects of 6-Times-Weekly Versus 3-Times-Weekly Hemodialysis on Depressive Symptoms and Self-reported Mental Health: Frequent Hemodialysis Network (FHN) Trials

    PubMed Central

    Unruh, Mark L.; Larive, Brett; Chertow, Glenn M; Eggers, Paul W.; Garg, Amit X.; Gassman, Jennifer; Tarallo, Maria; Finkelstein, Fredric O.; Kimmel, Paul L.

    2013-01-01

    Background Patients undergoing maintenance hemodialysis frequently exhibit poor mental health. We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health. Study Design 1-year randomized-controlled clinical trials. Setting & Participants Hemodialysis centers in the United States and Canada. A total of 332 patients were randomized to frequent (six times per week) as compared with conventional (three times per week) hemodialysis in the Frequent Hemodialysis Network (FHN) Daily (n=245) and Nocturnal (n=87) Trials. Intervention Daily Trial was a trial of frequent (six times per week), as compared with conventional (three times per week) in-center hemodialysis. The Nocturnal Trial assigned patients to either frequent nocturnal hemodialysis (six times per week) or conventional hemodialysis (three times per week). Outcomes Self-reported depressive symptoms and mental health. Measurements Beck Depression Inventory (BDI) and the mental health composite (MHC) score and emotional subscale of the RAND 36-Item Health Survey at baseline, 4 and 12 months. The MHC score is derived by summarizing these domains of the RAND 36-Item Health Survey: emotional, role emotional, energy/fatigue, and social functioning scales. Results In the Daily Trial, subjects randomized to frequent as compared with conventional in-center hemodialysis demonstrated no significant change over 12 months in adjusted mean BDI (−1.9 ± 0.7 vs. −0.6 ± 0.7; p=0.2), but experienced clinically significant improvements in adjusted mean MHC (3.7 ± 0.9 vs. 0.2 ± 1.0; P<0.01) and the emotional subscale (5.2 ± 1.6 vs. −0.3 ± 1.7; p=0.01). In the Nocturnal Trial, there were no significant changes among subjects randomized to nocturnal as compared with conventional hemodialysis on the same metrics. Limitations The trial interventions were not blinded. Conclusions Frequent in-center hemodialysis, as compared with conventional in

  12. Optimal cycling time trial position models: aerodynamics versus power output and metabolic energy.

    PubMed

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

    2014-06-01

    The aerodynamic drag of a cyclist in time trial (TT) position is strongly influenced by the torso angle. While decreasing the torso angle reduces the drag, it limits the physiological functioning of the cyclist. Therefore the aims of this study were to predict the optimal TT cycling position as function of the cycling speed and to determine at which speed the aerodynamic power losses start to dominate. Two models were developed to determine the optimal torso angle: a 'Metabolic Energy Model' and a 'Power Output Model'. The Metabolic Energy Model minimised the required cycling energy expenditure, while the Power Output Model maximised the cyclists׳ power output. The input parameters were experimentally collected from 19 TT cyclists at different torso angle positions (0-24°). The results showed that for both models, the optimal torso angle depends strongly on the cycling speed, with decreasing torso angles at increasing speeds. The aerodynamic losses outweigh the power losses at cycling speeds above 46km/h. However, a fully horizontal torso is not optimal. For speeds below 30km/h, it is beneficial to ride in a more upright TT position. The two model outputs were not completely similar, due to the different model approaches. The Metabolic Energy Model could be applied for endurance events, while the Power Output Model is more suitable in sprinting or in variable conditions (wind, undulating course, etc.). It is suggested that despite some limitations, the models give valuable information about improving the cycling performance by optimising the TT cycling position.

  13. Probiotic supplementation decreases intestinal transit time: Meta-analysis of randomized controlled trials

    PubMed Central

    Miller, Larry E; Ouwehand, Arthur C

    2013-01-01

    AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant key word combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001). Constipation (r2 = 39%, P = 0.01), higher mean age (r2 = 27%, P = 0.03), and higher percentage of female subjects (r2 = 23%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79) vs 0.17 (95%CI: -0.08-0.42), P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis) HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01) and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01) while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains. PMID:23922468

  14. The timing and duration of a sensitive period in human flavor learning: a randomized trial1234

    PubMed Central

    Mennella, Julie A; Lukasewycz, Laura D; Castor, Sara M; Beauchamp, Gary K

    2011-01-01

    Background: By using the response to protein hydrolysate formula (PHF) as a model system, we discovered the existence of a sensitive period, before 4 mo, when exposure determines the hedonic tone to flavors. Objective: We aimed to characterize the timing and duration of this sensitive period. Design: Healthy infants, whose parents had chosen formula feeding, were randomly assigned into 1 of 6 groups at age 0.5 mo: 2 control groups, one fed cow milk–based formula (CMF) and the other fed PHF for 7 mo; 2 groups fed PHF for either 1 or 3 mo beginning at 1.5 mo and CMF otherwise; and 2 groups fed PHF for 1 mo beginning at either 2.5 or 3.5 mo and CMF otherwise. Brief access taste tests were conducted monthly, and complete “meals” of both formulas occurred at the end of the study. Results: Three months of PHF exposure led to acceptance similar to that at 1 mo of exposure. Although these infants were more accepting than were infants with no exposure, they were less accepting than were infants with 7 mo of exposure, which suggests a dosing effect. The time when flavor experiences began was also significant. Among infants exposed to PHF for 1 mo, those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at younger ages. Conclusion: The general principles observed are likely of broader significance, indicating a fundamental feature of mammalian development and reflecting the importance of familiarizing infants with flavors that their mothers consume and transmit to breast milk. This trial was registered at clinicaltrials.gov as NCT00994747. PMID:21310829

  15. Effect of Heat and Heat Acclimatization on Cycling Time Trial Performance and Pacing

    PubMed Central

    RACINAIS, SEBASTIEN; PÉRIARD, JULIEN D.; KARLSEN, ANDERS; NYBO, LARS

    2015-01-01

    ABSTRACT Purpose This study aimed to determine the effects of heat acclimatization on performance and pacing during outdoor cycling time trials (TT, 43.4 km) in the heat. Methods Nine cyclists performed three TT in hot ambient conditions (TTH, approximately 37°C) on the first (TTH-1), sixth (TTH-2), and 14th (TTH-3) days of training in the heat. Data were compared with the average of two TT in cool condition (approximately 8°C) performed before and after heat acclimatization (TTC). Results TTH-1 (77 ± 6 min) was slower (P = 0.001) than TTH-2 (69 ± 5 min), and both were slower (P < 0.01) than TTC and TTH-3 (66 ± 3 and 66 ± 4 min, respectively), without differences between TTC and TTH-3 (P > 0.05). The cyclists initiated the first 20% of all TT at a similar power output, irrespective of climate and acclimatization status; however, during TTH-1, they subsequently had a marked decrease in power output, which was partly attenuated after 6 d of acclimatization and was further reduced after 14 d. HR was higher during the first 20% of TTH-1 than that in the other TT (P < 0.05), but there were no differences between conditions from 30% onward. Final rectal temperature was similar in all TTH (40.2°C ± 0.4°C, P = 1.000) and higher than that in TTC (38.5°C ± 0.6°C, P < 0.001). Conclusions After 2 wk of acclimatization, trained cyclists are capable of completing a prolonged TT in a similar time in the heat compared with cool conditions, whereas in the unacclimatized state, they experienced a marked decrease in power output during the TTH. PMID:24977692

  16. Cross-sectional study of Pfizer-sponsored clinical trials: assessment of time to publication and publication history

    PubMed Central

    Fay, Lorna

    2016-01-01

    Objective To estimate the proportion of Pfizer-sponsored clinical trials that completed in 2010 and are published as manuscripts in the peer-reviewed literature, and to assess the manuscript development history. Design Retrospective, cross-sectional analysis. Setting Clinical trials registered in ClinicalTrials.gov that completed in 2010 for approved, Pfizer prescription products in patients or vaccines in healthy participants. Main outcome measures The proportion of studies for which the primary outcome(s) was published and the median time from study completion to publication. The manuscript development history included the number of times a manuscript was submitted before it was accepted for publication. Results Among registered clinical trials for which Pfizer was the sponsor that completed in 2010, 76 met all inclusion criteria. The primary outcome(s) for 65 (85%) studies was published in 71 manuscripts; the median time to publication was 31 months (range 3–63 months). Of the remaining 11 studies, 2 had been submitted to at least one journal, 2 had not yet been submitted and 7 had no plans to publish because the study had terminated early due to recruitment challenges. Manuscripts accepted at the first choice journal were published at median time of 28 months (range 8–63, n=31), those accepted at second choice journal were published at 32 months (3–45, n=19), and for those accepted at third choice journal, it was 40 months (range 24–53, n=13). Conclusions The publication rate and median time to publication from study completion for Pfizer-sponsored studies were comparable to those previously reported for combined analyses of industry and non-industry sectors. Opportunities exist for sponsors, authors and journals to explore ideas that would facilitate more timely publication for clinical trial results. However, to be effective, such changes may need to revisit the entire publication process. PMID:27431904

  17. Positive effect of lower body compression garments on subsequent 40-kM cycling time trial performance.

    PubMed

    de Glanville, Kieran M; Hamlin, Michael J

    2012-02-01

    This study aimed to investigate the effect of wearing graduated compression garments during recovery on subsequent 40-km time trial performance. In a randomized single-blind crossover experiment, 14 trained multisport male athletes (mean ± SD: age 33.8 ± 6.8 years, 40-km time 66:11 ± 2:10 minutes:seconds) were given a graduated full-leg-length compressive garment (76% Meryl Elastane, 24% Lycra) or a similar-looking noncompressive placebo garment (92% Polyester, 8% Spandex) to wear continuously for 24 hours after performing an initial 40-km time trial in their normal cycling attire. After the 24-hour recovery period, the compression (or placebo) garments were removed, and a second 40-km time trial was then completed to gauge the effect of each garment on subsequent performance. One week later, the groups were reversed and testing procedures repeated. The participant's hydration status, nutritional intake, and training were similar before each set of trials. Performance time in the second time trial was substantially improved with compression compared with placebo garments (1.2 ± 0.4%, mean ± 90% confidence interval). This improvement resulted in a substantially higher average power output after wearing the compression garment compared with that after wearing the placebo garment (3.3 ± 1.1%). Differences in oxygen cost and rating of perceived exertion between groups were trivial or unclear. The wearing of graduated compressive garments during recovery is likely to be worthwhile and unlikely to be harmful for well-trained endurance athletes.

  18. Mouth Rinsing With Carbohydrate Solutions at the Postprandial State Fail to Improve Performance During Simulated Cycling Time Trials.

    PubMed

    Ispoglou, Theocharis; OʼKelly, Damian; Angelopoulou, Athanasia; Bargh, Melissa; OʼHara, John P; Duckworth, Lauren C

    2015-08-01

    Mouth rinsing with carbohydrate (CHO) solutions during cycling time trials results in performance enhancements; however, most studies have used approximately 6% CHO solutions. Therefore, the purpose of this study was to compare the effectiveness of mouth rinsing with 4, 6, and 8% CHO solutions on 1-hour simulated cycling time trial performance. On 4 occasions, 7 trained male cyclists completed at the postprandial period, a set amount of work as fast as possible in a randomized counterbalanced order. The subjects rinsed their mouth for 5 seconds, on completion of each 12.5% of the trial, with 25 ml of a non-CHO placebo and 4, 6, and 8% CHO solutions. No additional fluids were consumed during the time trial. Heart rate (HR), ratings of perceived exertion (RPE), thirst (TH), and subjective feelings (SF) were recorded after each rinse. Furthermore, blood samples were drawn every 25% of the trial to measure blood glucose and blood lactate concentrations, whereas whole-body CHO oxidation was monitored continuously. Time to completion was not significant between conditions with the placebo, 4, 6, and 8% conditions completing the trials in 62.0 ± 3.0, 62.8 ± 4.0, 63.4 ± 3.4, and 63 ± 4.0 minutes, respectively. There were no significant differences between conditions in any of the variables mentioned above; however, significant time effects were observed for HR, RPE, TH, and SF. Post hoc analysis showed that TH and SF of subjects in the CHO conditions but not in the placebo were significantly increased by completion of the time trial. In conclusion, mouth rinsing with CHO solutions did not impact 1-hour cycling performance in the postprandial period and in the absence of fluid intake. Our findings suggest that there is scope for further research to explore the activation regions of the brain and whether they are receptive to CHO dose, before specific recommendations for athletic populations are established. Consequently, mouth rinsing as a practical strategy for coaches

  19. Analysis of Classical Time-Trial Performance and Technique-Specific Physiological Determinants in Elite Female Cross-Country Skiers.

    PubMed

    Sandbakk, Øyvind; Losnegard, Thomas; Skattebo, Øyvind; Hegge, Ann M; Tønnessen, Espen; Kocbach, Jan

    2016-01-01

    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. PMID:27536245

  20. Analysis of Classical Time-Trial Performance and Technique-Specific Physiological Determinants in Elite Female Cross-Country Skiers

    PubMed Central

    Sandbakk, Øyvind; Losnegard, Thomas; Skattebo, Øyvind; Hegge, Ann M.; Tønnessen, Espen; Kocbach, Jan

    2016-01-01

    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. PMID:27536245

  1. Analysis of Classical Time-Trial Performance and Technique-Specific Physiological Determinants in Elite Female Cross-Country Skiers.

    PubMed

    Sandbakk, Øyvind; Losnegard, Thomas; Skattebo, Øyvind; Hegge, Ann M; Tønnessen, Espen; Kocbach, Jan

    2016-01-01

    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.

  2. Effects of magnitude and frequency of variations in external power output on simulated cycling time-trial performance.

    PubMed

    Wells, Marc; Atkinson, Greg; Marwood, Simon

    2013-01-01

    Mechanical models of cycling time-trial performance have indicated adverse effects of variations in external power output on overall performance times. Nevertheless, the precise influences of the magnitude and number of these variations over different distances of time trial are unclear. A hypothetical cyclist (body mass 70 kg, bicycle mass 10 kg) was studied using a mathematical model of cycling, which included the effects of acceleration. Performance times were modelled over distances of 4-40 km, mean power outputs of 200-600 W, power variation amplitudes of 5-15% and variation frequencies of 2-32 per time-trial. Effects of a "fast-start" strategy were compared with those of a constant-power strategy. Varying power improved 4-km performance at all power outputs, with the greatest improvement being 0.90 s for ± 15% power variation. For distances of 16.1, 20 and 40 km, varying power by ± 15% increased times by 3.29, 4.46 and 10.43 s respectively, suggesting that in long-duration cycling in constant environmental conditions, cyclists should strive to reduce power variation to maximise performance. The novel finding of the present study is that these effects are augmented with increasing event distance, amplitude and period of variation. These two latter factors reflect a poor adherence to a constant speed.

  3. METHODS AND BASELINE CARDIOVASCULAR DATA FROM THE EARLY VERSUS LATE INTERVENTION TRIAL WITH ESTRADIOL TESTING THE MENOPAUSAL HORMONE TIMING HYPOTHESIS

    PubMed Central

    Hodis, Howard N.; Mack, Wendy J.; Shoupe, Donna; Azen, Stanley P.; Stanczyk, Frank Z.; Hwang-Levine, Juliana; Budoff, Matthew J.; Henderson, Victor W.

    2014-01-01

    Objective To present methods and baseline data from the Early versus Late Intervention Trial with Estradiol (ELITE), the only clinical trial designed to specifically test the timing hypothesis of postmenopausal hormone therapy (HT). The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time-since-menopause. Methods ELITE is a randomized, double-blinded, placebo-controlled trial with a 2x2 factorial design. 643 healthy postmenopausal women without cardiovascular disease were randomized to oral estradiol or placebo for up to 6-7 years according to number of years-since-menopause, <6 years or ≥10 years. Carotid artery intima-media thickness (CIMT) and cardiac computed tomography were conducted to determine HT effects on subclinical atherosclerosis across menopause strata. Results Participants in the early and late postmenopausal strata were well-separated by mean age, 55.4 versus 65.4 years and median time-since-menopause, 3.5 versus 14.3 years, respectively. The expected risk factors were associated with CIMT at baseline in both strata (age, blood pressure and body mass index). In the early but not in the late postmenopausal group, there were significant associations between CIMT and factors that may play a role in responsiveness of atherosclerosis progression according to timing of HT initiation. These include LDL-C, HDLC, sex hormone binding globulin and serum total estradiol. Conclusion The ELITE randomized controlled trial is timely and unique. Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease. (NCT00114517; www.clinicaltrials.gov) PMID:25380275

  4. Effect of Sodium Phosphate Supplementation on Cycling Time Trial Performance and VO2 1 and 8 Days Post Loading

    PubMed Central

    Brewer, Cameron P.; Dawson, Brian; Wallman, Karen E.; Guelfi, Kym J.

    2014-01-01

    This study examined the effect of 6 days of sodium phosphate (SP) (50 mg·kg·FFM-1·day-1) or placebo (PL) supplementation in trained cyclists on either 100 kJ (23.9 Kcal) (~3-4 min) or 250 kJ (59.7 Kcal) (~10-12 min) time trials performances both 1 and 8 days post-supplementation. Trials were performed in a counterbalanced crossover design, with a 28-day washout period between supplementation phases. No significant differences, moderate-large ES (d) or likely (or greater) smallest worthwhile change (SWC) values were recorded for time to completion and mean power output on days 1 and 8 post-supplementation, both within and between SP and PL for either the 100 or 250 kJ (23.9 or 59.7 Kcal) trials. In the 100 kJ (23.9 Kcal) trial (only) first minute VO2 tended to be higher in SP8 than both PL8 (d = 0.60; 88/10/2 SWC) and SP1 (d = 0.47: 82/15/3 SWC), as was mean VO2 (PL8: d = 0.77; 93/6/1 SWC and SP1: d = 0.84; 90/8/3 SWC). No significant differences were found for heart rate, ratings of perceived exertion and blood lactate post-exercise within or between any trials, while serum phosphate values were not different before or after supplementation with SP or PL. In conclusion, this study showed a tendency for increased VO2 in a short duration (100 kJ/ 23.9 Kcal: ~3-4 min) cycling test on day 8 after SP supplementation, but no differences in 100 or 250 kJ (23.9 or 59.7 Kcal) time trials performances were observed. Key Points Studies investigating the effects of sodium phosphate loading on shorter duration (<15 min) and higher intensity exercise performance are lacking, as is research on how long any ergogenic effect may last. Loading did not improve cycling time trial (~3-4 min and 10-12 min) performance either 1 or 8 days after supplementation. Future studies should investigate the effect of sodium phosphate loading on repeated sprints and simulated cycling road race performance over extended durations (>30 min), where it may be likely to have a more beneficial effect

  5. Vastus medialis muscle oxygenation trends during a simulated 20-km cycle time trial.

    PubMed

    Neary, J P; Hall, K; Bhambhani, Y N

    2001-09-01

    In this study we examined the oxygenation trend of the vastus medialis muscle during sustained high-intensity exercise. Ten cyclists performed an incremental cycle ergometer test to voluntary exhaustion [mean (SD) maximum oxygen uptake 4.29 (0.63) l x min(-1); relative to body mass 60.8 (2.4) ml x kg(-1)min(-1)] and a simulated 20-km time trial (20TT) on a wind-loaded roller system using their own bicycle (group time = 23-31 min) in two separate sessions. Cardiorespiratory responses were monitored using an automated metabolic cart and a wireless heart rate monitor. Tissue absorbency, which was used as an index of muscle oxygenation, was recorded simultaneously from the vastus medialis using near-infrared spectroscopy. Group mean values for oxygen uptake, ventilation, heart rate, respiratory exchange ratio, power output, and rating of perceived exhaustion were significantly (P < or = 0.05) higher during the incremental test compared to the 20TT [4.29 (0.63) l x min(-1) vs 4.01 (0.55) l x min(-1), 120.4 (26) l x min(-1) vs 97.6 (16.1) l x min(-1), 195 (8) beats x min(-1) vs 177 (9) beats min(-1), 1.15 (0.06) vs 0.93 (0.06), 330.1 (31) W vs 307.2 (24.5) W, and 19 (1.5) vs 16 (1.7), respectively]. Oxygen uptake and heart rate during the 20TT corresponded to 93.5% and 90.7%, respectively, of the maximal values observed during the incremental test. Comparison of the muscle oxygenation trends between the two tests indicated a significantly greater degree of deoxygenation during the 20TT [-699 (250) mV vs 439 (273) mV; P < or = 0.05] and a significant delay in the recovery oxygenation from the 20TT. The mismatching of whole-body oxygen uptake and localised tissue oxygenation between the two tests could be due to differences in muscle temperature, pH, localised blood flow and motor unit recruitment patterns between the two tests.

  6. Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial

    PubMed Central

    Bourdillon, Nicolas; Fan, Jui-Lin; Uva, Barbara; Müller, Hajo; Meyer, Philippe; Kayser, Bengt

    2015-01-01

    Background: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. Methods: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. Results: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). Conclusion: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia. PMID:26528189

  7. Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models

    PubMed Central

    Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P.

    2016-01-01

    In a phase III multi-center cancer clinical trial or large public health studies, sample size is predetermined to achieve desired power and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date based on the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of NSABP trial B-38. The results showed that application of proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. PMID:22411544

  8. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  9. Randomised Trials or the Test of Time? The Story of Human Albumin Administration.

    ERIC Educational Resources Information Center

    Roberts, Ian

    2000-01-01

    Conducted a systematic review of randomized controlled trials of the administration of human albumin in critically ill patients. Findings raised serious concerns about the safety of an intervention that has been widely used in health care around the world. Findings illustrate the importance of systematic reviews in health care and other areas of…

  10. Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: A multivariate meta-analysis examining change over time

    PubMed Central

    Del Re, AC; Maisel, Natalya; Blodgett, Janet; Wilbourne, Paula; Finney, John

    2014-01-01

    Objective Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. Method Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. Results Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. Conclusion Similar to previous pharmacotherapy placebo research, substantial pre- to post-test placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time. PMID:23857312

  11. Time-to-event continual reassessment method incorporating treatment cycle information with application to an oncology phase I trial.

    PubMed

    Huang, Bo; Kuan, Pei Fen

    2014-11-01

    Delayed dose limiting toxicities (i.e. beyond first cycle of treatment) is a challenge for phase I trials. The time-to-event continual reassessment method (TITE-CRM) is a Bayesian dose-finding design to address the issue of long observation time and early patient drop-out. It uses a weighted binomial likelihood with weights assigned to observations by the unknown time-to-toxicity distribution, and is open to accrual continually. To avoid dosing at overly toxic levels while retaining accuracy and efficiency for DLT evaluation that involves multiple cycles, we propose an adaptive weight function by incorporating cyclical data of the experimental treatment with parameters updated continually. This provides a reasonable estimate for the time-to-toxicity distribution by accounting for inter-cycle variability and maintains the statistical properties of consistency and coherence. A case study of a First-in-Human trial in cancer for an experimental biologic is presented using the proposed design. Design calibrations for the clinical and statistical parameters are conducted to ensure good operating characteristics. Simulation results show that the proposed TITE-CRM design with adaptive weight function yields significantly shorter trial duration, does not expose patients to additional risk, is competitive against the existing weighting methods, and possesses some desirable properties.

  12. Prior exercise reduces fast-start duration and end-spurt magnitude during cycling time-trial.

    PubMed

    Lima-Silva, A E; Correia-Oliveira, C R; Tenorio, L; Melo, A A; Bertuzzi, R; Bishop, D

    2013-08-01

    We examined the pacing strategy and the magnitude of the end spurt during a 200-kJ cycling time trial performed 12-14 h after an exercise protocol designed to reduce muscle glycogen content. 9 physically-active men performed 5 familiarization sessions and 2 experimental 200-kJ time trials in either a control condition (CON) or after an exercise protocol performed the previous evening that was designed to induce muscle glycogen depletion (EP). Mean total time was faster and power output was higher in the CON than in the EP (P<0.01). A fast-start was maintained until the 50-kJ section in CON, but only the 25-kJ section for EP (P<0.05). The power outputs during the 50-, 150- and 200-kJ sections, and the magnitude of the end-spurt, were significantly higher for the CON than for the EP condition (P<0.05). There was no significant difference in the rating of perceived exertion (overall feeling and feeling in legs) between conditions. In conclusion, a protocol designed to decrease muscle glycogen stores reduced the duration of the fast-start and the magnitude of the end spurt during a 200-kJ cycling time trial, impairing the overall performance.

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

    PubMed Central

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

    2016-01-01

    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 < 0.007) and was evident 5 min post-TT during cycling (11.2 ± 2.6 and 8.8 ± 3.2 mmol/L; p = 0.001) and handcycling (10.6 ± 2.5 and 9.2 ± 2.9 mmol/L; p = 0.006). Lower overall ratings of perceived exertion (RPE) were seen following CAF during the preload (p < 0.05) but not post-TT. Lower peripheral RPE were reported at 20 min during cycling and at 30 min during handcycling, and lower central RPE was seen at 30 min during cycling (p < 0.05). 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. PMID:27348000

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

    PubMed

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

    2016-01-01

    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 < 0.007) and was evident 5 min post-TT during cycling (11.2 ± 2.6 and 8.8 ± 3.2 mmol/L; p = 0.001) and handcycling (10.6 ± 2.5 and 9.2 ± 2.9 mmol/L; p = 0.006). Lower overall ratings of perceived exertion (RPE) were seen following CAF during the preload (p < 0.05) but not post-TT. Lower peripheral RPE were reported at 20 min during cycling and at 30 min during handcycling, and lower central RPE was seen at 30 min during cycling (p < 0.05). 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. PMID:27348000

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

    PubMed

    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 < 0.007) and was evident 5 min post-TT during cycling (11.2 ± 2.6 and 8.8 ± 3.2 mmol/L; p = 0.001) and handcycling (10.6 ± 2.5 and 9.2 ± 2.9 mmol/L; p = 0.006). Lower overall ratings of perceived exertion (RPE) were seen following CAF during the preload (p < 0.05) but not post-TT. Lower peripheral RPE were reported at 20 min during cycling and at 30 min during handcycling, and lower central RPE was seen at 30 min during cycling (p < 0.05). 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.

  16. The EuroNet paediatric hodgkin network - modern imaging data management for real time central review in multicentre trials.

    PubMed

    Kurch, L; Mauz-Körholz, C; Bertling, S; Wallinder, M; Kaminska, M; Marwede, D; Tchavdarova, L; Georgi, T W; Elsner, A; Barthel, A; Stoevesandt, D; Hasenclever, D; Sattler, B; Sabri, O; Körholz, D; Kluge, R

    2013-11-01

    Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review.

  17. 3D constraints on a possible deep > 2.5 km massive sulphide mineralization from 2D crooked-line seismic reflection data in the Kristineberg mining area, northern Sweden

    NASA Astrophysics Data System (ADS)

    Malehmir, Alireza; Schmelzbach, Cedric; Bongajum, Emmanuel; Bellefleur, Gilles; Juhlin, Christopher; Tryggvason, Ari

    2009-12-01

    2D crooked-line seismic reflection surveys in crystalline environments are often considered challenging in their processing and interpretation. These challenges are more evident when complex diffraction signals that can originate from out-of-the-plane and a variety of geological features are present. A seismic profile in the Kristineberg mining area in northern Sweden shows an impressive diffraction package, covering an area larger than 25 km 2 in the subsurface at depths greater than 2.5 km. We present here a series of scenarios in which each can, to some extent, explain the nature of this extraordinarily large package of diffractions. Cross-dip analysis, diffraction imaging and modeling, as well as 3D processing of the crooked-line data provided constraints on the interpretation of the diffraction package. Overall, the results indicate that the diffraction package can be associated with at least four main short south-dipping diffractors in a depth range of 2.5-4.5 km. Candidate scenarios for the origin of the diffraction package are: (1) a series of massive sulphide deposits, (2) a series of mafic-ultramafic intrusions, (3) a major shear-zone and (4) multiple contact lithologies. We have also investigated the possible contribution of mode-converted scattered energy in the diffraction package using a modified converted-wave 3D prestack depth migration algorithm with the results indicating that a majority of the diffractions are P-wave diffractions. The 3D prestack migration of the data provided improved images of a series of steeply north-dipping mafic-ultramafic sill intrusions to a depth of about 4 km, where the diffractions appear to focus after the migration. The results and associated interpretations presented in this paper have improved our understanding of this conspicuous package of diffractions and may lead to re-evaluation of the 3D geological model of the Kristineberg mining area.

  18. Scaling maximal oxygen uptake to predict cycling time-trial performance in the field: a non-linear approach.

    PubMed

    Nevill, A M; Jobson, S A; Palmer, G S; Olds, T S

    2005-08-01

    The purpose of the present article is to identify the most appropriate method of scaling VO2max for differences in body mass when assessing the energy cost of time-trial cycling. The data from three time-trial cycling studies were analysed (N = 79) using a proportional power-function ANCOVA model. The maximum oxygen uptake-to-mass ratio found to predict cycling speed was VO2max(m)(-0.32) precisely the same as that derived by Swain for sub-maximal cycling speeds (10, 15 and 20 mph). The analysis was also able to confirm a proportional curvilinear association between cycling speed and energy cost, given by (VO2max(m)(-0.32))0.41. The model predicts, for example, that for a male cyclist (72 kg) to increase his average speed from 30 km h(-1) to 35 km h(-1), he would require an increase in VO2max from 2.36 l min(-1) to 3.44 l min(-1), an increase of 1.08 l min(-1). In contrast, for the cyclist to increase his mean speed from 40 km h(-1) to 45 km h(-1), he would require a greater increase in VO2max from 4.77 l min(-1) to 6.36 l min(-1), i.e. an increase of 1.59 l min(-1). The model is also able to accommodate other determinants of time-trial cycling, e.g. the benefit of cycling with a side wind (5% faster) compared with facing a predominately head/tail wind (P<0.05). Future research could explore whether the same scaling approach could be applied to, for example, alternative measures of recording power output to improve the prediction of time-trial cycling performance.

  19. The potential influence of perception of achievement on performance in volitional time-to-exhaustion cycle ergometer trials.

    PubMed

    Lorimer, Ross; Babraj, John

    2013-06-01

    The purpose of this short communication was to report the findings of an investigation of the potential influence of spontaneous goal setting on subjects undertaking maximal fitness testing. Subjects were asked to complete a single incremental volitional time-to-exhaustion cycle ergometer trial. The final minute of the trial, after the last increase in increment in resistance, was broken down into six 10-second intervals and a frequency count made of how many subjects stopped within each interval. A chi-square test was used to determine that there was a significant difference between the expected and the observed frequencies (p < 0.05), with 45% of subjects stopping in the first interval (0-10 seconds) and 0% within the last interval (51-60 seconds). Reflections of the subjects revealed that those who were close to exhaustion but near to reaching the next increment of resistance were more likely to "push on." However, despite having been told to keep going as long as they could, subjects upon reaching that increment stopped almost immediately as they believed they could not manage to reach the next increment. This suggests a potential psychological element related to goal achievement that influences performance in incremental volitional time-to-exhaustion cycle ergometer trials. Practically, this means that the information participants have available on which to base goals (level of increment, time, etc.) needs to be minimized to prevent spontaneous goal setting.

  20. Effect of a carbohydrate mouth rinse on simulated cycling time-trial performance commenced in a fed or fasted state.

    PubMed

    Lane, Stephen C; Bird, Stephen R; Burke, Louise M; Hawley, John A

    2013-02-01

    It is presently unclear whether the reported ergogenic effect of a carbohydrate (CHO) mouth rinse on cycling time-trial performance is affected by the acute nutritional status of an individual. Hence, the aim of this study was to investigate the effect of a CHO mouth rinse on a 60-min simulated cycling time-trial performance commenced in a fed or fasted state. Twelve competitive male cyclists each completed 4 experimental trials using a double-blinded Latin square design. Two trials were commenced 2 h after a meal that contained 2.5 g·kg(-1) body mass of CHO (FED) and 2 after an overnight fast (FST). Prior to and after every 12.5% of total time during a performance ride, either a 10% maltodextrin (CHO) or a taste-matched placebo (PLB) solution was mouth rinsed for 10 s then immediately expectorated. There were significant main effects for both pre-ride nutritional status (FED vs. FST; p < 0.01) and CHO mouth rinse (CHO vs. PLB; p < 0.01) on power output with an interaction evident between the interventions (p < 0.05). The CHO mouth rinse improved mean power to a greater extent after an overnight fast (282 vs. 273 W, 3.4%; p < 0.01) compared with a fed state (286 vs. 281 W, 1.8%; p < 0.05). We concluded that a CHO mouth rinse improved performance to a greater extent in a fasted compared with a fed state; however, optimal performance was achieved in a fed state with the addition of a CHO mouth rinse.

  1. Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

    PubMed Central

    Ali, Asad; Kazi, Abdul Momin; Cortese, Margaret M.; Fleming, Jessica A.; Moon, SungSil; Parashar, Umesh D.; Jiang, Baoming; McNeal, Monica M.; Steele, Duncan; Bhutta, Zulfiqar; Zaidi, Anita K. M.

    2015-01-01

    Background Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration. Methods Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective). Results Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005). Conclusions Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a

  2. Preventive home visits postpone mortality – a controlled trial with time-limited results

    PubMed Central

    Sahlen, Klas-Göran; Dahlgren, Lars; Hellner, Britt Mari; Stenlund, Hans; Lindholm, Lars

    2006-01-01

    Background There is a debate on whether preventive home visits to older people have any impact. This study was undertaken to investigate whether preventive home visits by professional health workers to older persons can postpone mortality in a Swedish context. Method A controlled trial in a small community in the north of Sweden. Participants are healthy pensioners aged 75 years and over. 196 pensioners were selected as the intervention group and 346 as the control group. The intervention, two visits per year, lasted two years. Results During the intervention, mortality was 27 per 1000 in the intervention group and 48 per 1000 in the control group. The incidence rate ratio for the control group IR2000–2001 was 1,79 (95%CI = 0,94–3,40). Analysing the data with an "on treatment approach" gave a significant result, 2,31 (95%CI = 1,07–5,02) After the trial the difference between the groups disappeared. Conclusion Preventive home visits in a healthy older population can postpone mortality in a Swedish context if they are carried out by professional health-workers in a structured way. When the home visit programme ended the effect on mortality disappeared. These findings are dependent on contextual factors that make it difficult to form general policy recommendations. PMID:16945128

  3. Joint modeling tumor burden and time to event data in oncology trials.

    PubMed

    Shen, Ye; Anderson, Aparna; Sinha, Ritwik; Li, Yang

    2014-01-01

    The tumor burden (TB) process is postulated to be the primary mechanism through which most anticancer treatments provide benefit. In phase II oncology trials, the biologic effects of a therapeutic agent are often analyzed using conventional endpoints for best response, such as objective response rate and progression-free survival, both of which causes loss of information. On the other hand, graphical methods including spider plot and waterfall plot lack any statistical inference when there is more than one treatment arm. Therefore, longitudinal analysis of TB data is well recognized as a better approach for treatment evaluation. However, longitudinal TB process suffers from informative missingness because of progression or death. We propose to analyze the treatment effect on tumor growth kinetics using a joint modeling framework accounting for the informative missing mechanism. Our approach is illustrated by multisetting simulation studies and an application to a nonsmall-cell lung cancer data set. The proposed analyses can be performed in early-phase clinical trials to better characterize treatment effect and thereby inform decision-making. PMID:25044957

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

    PubMed Central

    Berardi, John M; Noreen, Eric E; Lemon, Peter WR

    2008-01-01

    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. PMID:19108717

  5. Randomised clinical trial to determine optimum initiation time of norgestrel-progestin only contraception in Eldoret Teaching Hospital, Kenya.

    PubMed

    Were, E O; Kendall, J Z; Nyongesa, P

    1997-02-01

    In a randomised controlled trial to determine the optimum time of initiation of Ovrette, a progestin only oral contraceptive among postpartum women, who fully or nearly fully breast-fed their infants in the first six months, no difference was found between group 1 (initiating at six weeks postpartum) and group 2 (initiating the pill at return of menses or 6 months postpartum). There were no pregnancies in either group during the 18 month follow-up. There were no significant differences in the continuation rates between the two group.

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

    PubMed

    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.

  7. Statistics in review. Part 2: generalised linear models, time-to-event and time-series analysis, evidence synthesis and clinical trials.

    PubMed

    Moran, John L; Solomon, Patricia J

    2007-06-01

    In Part I, we reviewed graphical display and data summary, followed by a consideration of linear regression models. Generalised linear models, structured in terms of an exponential response distribution and link function, are now introduced, subsuming logistic and Poisson regression. Time-to-event ("survival") analysis is developed from basic principles of hazard rate, and survival, cumulative distribution and density functions. Semi-parametric (Cox) and parametric (accelerated failure time) regression models are contrasted. Time-series analysis is explicated in terms of trend, seasonal, and other cyclical and irregular components, and further illustrated by development of a classical Box-Jenkins ARMA (autoregressive moving average) model for monthly ICU-patient hospital mortality rates recorded over 11 years. Multilevel (random-effects) models and principles of meta-analysis are outlined, and the review concludes with a brief consideration of important statistical aspects of clinical trials: sample size determination, interim analysis and "early stopping".

  8. Real-Time Fatigue Reduction in Emergency Care Clinicians: The SleepTrackTXT Randomized Trial

    PubMed Central

    Patterson, P. Daniel; Buysse, Daniel J.; Weaver, Matthew D.; Doman, Jack M.; Moore, Charity G.; Suffoletto, Brian P.; McManigle, Kyle L.; Callaway, Clifton W.; Yealy, Donald M.

    2015-01-01

    Background We assessed performance characteristics and impact of a mobile phone text-message intervention for reducing intra-shift fatigue among emergency clinician shift workers. Methods We used a randomized controlled trial of 100 participants. All participants received text-message assessments at the start, every 4-hours during, and at end of scheduled shifts over a 90-day period. Text-message queries measured self-rated sleepiness, fatigue, and difficulty with concentration. Additional text-messages were sent to intervention participants to promote alertness. A performance measure of interest was compliance with answering text-messages. Results Ninety-nine participants documented 2,621 shifts and responded to 36,073 of 40,947 text-messages (88% compliance rate). Intervention participants reported lower mean fatigue and sleepiness at 4 hours, 8 hours, and at the end of 12-hour shifts compared to controls (p<0.05). Intervention participants reported better sleep quality at 90-days compared to baseline (p=0.01). Conclusions We showed feasibility and short-term efficacy of a text-message based assessment and intervention tool. PMID:26305869

  9. Predictions of future dangerousness in capital murder trials: is it time to "disinvent the wheel"?

    PubMed

    Edens, John F; Buffington-Vollum, Jacqueline K; Keilen, Andrea; Roskamp, Phillip; Anthony, Christine

    2005-02-01

    Although recent U.S. Supreme Court decisions regarding the death penalty (e.g., Atkins v. Virginia, 2002) have renewed interest in mental health issues, one topic that has not received much attention recently is the ongoing use of expert testimony to support claims that defendants represent a "continuing threat to society." In this article, we (a) review prior research relevant to determining the accuracy of clinical predictions that capital defendants will commit future acts of criminal violence; (b) summarize new data from current and former death row inmates in Texas that bolster the claim that such predictions are gross overestimates of risk; and (c) review extant research addressing the potential utility of various risk assessment instruments that increasingly are being used to reinforce clinical predictions in capital trials. Despite significant recent advances in the field of risk assessment, clinical assertions that a defendant is likely to commit future violent acts appear to be highly inaccurate and ethically questionable at best. Moreover, available research offers little support for the claim that the accuracy of these predictions will be appreciably improved by relying on more structured risk assessment measures that have some demonstrated predictive validity in other contexts.

  10. Timing and extent of response in colorectal cancer: critical review of current data and implication for future trials

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Bonotto, Marta; Rihawi, Karim; Lutrino, Stefania Eufemia; Ferrari, Laura; Casagrande, Mariaelena; Ongaro, Elena; Berretta, Massimiliano; Avallone, Antonio; Rosati, Gerardo; Giuliani, Francesco; Fasola, Gianpiero

    2015-01-01

    The identification of new surrogate endpoints for advanced colorectal cancer is becoming crucial and, along with drug development, it represents a research field increasingly studied. Although overall survival (OS) remains the strongest trial endpoint available, it requires larger sample size and longer periods of time for an event to happen. Surrogate endpoints such as progression free survival (PFS) or response rate (RR) may overcome these issues but, as such, they need to be prospectively validated before replacing the real endpoints; moreover, they often bear many other limitations. In this narrative review we initially discuss the role of time-to-event endpoints, objective response and response rate as surrogates of OS in the advanced colorectal cancer setting, discussing also how such measures are influenced by the tumor assessment criteria currently employed. We then report recent data published about early tumor shrinkage and deepness of response, which have recently emerged as novel potential endpoint surrogates, discussing their strengths and weaknesses and providing a critical comment. Despite being very compelling, the role of such novel response measures is yet to be confirmed and their surrogacy with OS still needs to be further investigated within larger and well-designed trials. PMID:26308250

  11. Relieving thermal discomfort: Effects of sprayed L-menthol on perception, performance, and time trial cycling in the heat.

    PubMed

    Barwood, M J; Corbett, J; Thomas, K; Twentyman, P

    2015-06-01

    L-menthol stimulates cutaneous thermoreceptors and induces cool sensations improving thermal comfort, but has been linked to heat storage responses; this could increase risk of heat illness during self-paced exercise in the heat. Therefore, L-menthol application could lead to a discrepancy between behavioral and autonomic thermoregulatory drivers. Eight male participants volunteered. They were familiarized and then completed two trials in hot conditions (33.5 °C, 33% relative humidity) where their t-shirt was sprayed with CONTROL-SPRAY or MENTHOL-SPRAY after 10 km (i.e., when they were hot and uncomfortable) of a 16.1-km cycling time trial (TT). Thermal perception [thermal sensation (TS) and comfort (TC)], thermal responses [rectal temperature (Trec ), skin temperature (Tskin )], perceived exertion (RPE), heart rate, pacing (power output), and TT completion time were measured. MENTHOL-SPRAY made participants feel cooler and more comfortable and resulted in lower RPE (i.e., less exertion) yet performance was unchanged [TT completion: CONTROL-SPRAY 32.4 (2.9) and MENTHOL-SPRAY 32.7 (3.0) min]. Trec rate of increase was 1.40 (0.60) and 1.45 (0.40) °C/h after CONTROL-SPRAY and MENTHOL-SPRAY application, which were not different. Spraying L-menthol toward the end of self-paced exercise in the heat improved perception, but did not alter performance and did not increase heat illness risk.

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

    SciTech Connect

    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

    2009-11-15

    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.

  13. Timing and extent of response in colorectal cancer: critical review of current data and implication for future trials.

    PubMed

    Aprile, Giuseppe; Fontanella, Caterina; Bonotto, Marta; Rihawi, Karim; Lutrino, Stefania Eufemia; Ferrari, Laura; Casagrande, Mariaelena; Ongaro, Elena; Berretta, Massimiliano; Avallone, Antonio; Rosati, Gerardo; Giuliani, Francesco; Fasola, Gianpiero

    2015-10-01

    The identification of new surrogate endpoints for advanced colorectal cancer is becoming crucial and, along with drug development, it represents a research field increasingly studied. Although overall survival (OS) remains the strongest trial endpoint available, it requires larger sample size and longer periods of time for an event to happen. Surrogate endpoints such as progression free survival (PFS) or response rate (RR) may overcome these issues but, as such, they need to be prospectively validated before replacing the real endpoints; moreover, they often bear many other limitations. In this narrative review we initially discuss the role of time-to-event endpoints, objective response and response rate as surrogates of OS in the advanced colorectal cancer setting, discussing also how such measures are influenced by the tumor assessment criteria currently employed. We then report recent data published about early tumor shrinkage and deepness of response, which have recently emerged as novel potential endpoint surrogates, discussing their strengths and weaknesses and providing a critical comment. Despite being very compelling, the role of such novel response measures is yet to be confirmed and their surrogacy with OS still needs to be further investigated within larger and well-designed trials. PMID:26308250

  14. Detrended fluctuation analysis and adaptive fractal analysis of stride time data in Parkinson's disease: stitching together short gait trials.

    PubMed

    Kirchner, Marietta; Schubert, Patric; Liebherr, Magnus; Haas, Christian T

    2014-01-01

    Variability indicates motor control disturbances and is suitable to identify gait pathologies. It can be quantified by linear parameters (amplitude estimators) and more sophisticated nonlinear methods (structural information). Detrended Fluctuation Analysis (DFA) is one method to measure structural information, e.g., from stride time series. Recently, an improved method, Adaptive Fractal Analysis (AFA), has been proposed. This method has not been applied to gait data before. Fractal scaling methods (FS) require long stride-to-stride data to obtain valid results. However, in clinical studies, it is not usual to measure a large number of strides (e.g., [Formula: see text][Formula: see text] strides). Amongst others, clinical gait analysis is limited due to short walkways, thus, FS seem to be inapplicable. The purpose of the present study was to evaluate FS under clinical conditions. Stride time data of five self-paced walking trials ([Formula: see text] strides each) of subjects with PD and a healthy control group (CG) was measured. To generate longer time series, stride time sequences were stitched together. The coefficient of variation (CV), fractal scaling exponents [Formula: see text] (DFA) and [Formula: see text] (AFA) were calculated. Two surrogate tests were performed: A) the whole time series was randomly shuffled; B) the single trials were randomly shuffled separately and afterwards stitched together. CV did not discriminate between PD and CG. However, significant differences between PD and CG were found concerning [Formula: see text] and [Formula: see text]. Surrogate version B yielded a higher mean squared error and empirical quantiles than version A. Hence, we conclude that the stitching procedure creates an artificial structure resulting in an overestimation of true [Formula: see text]. The method of stitching together sections of gait seems to be appropriate in order to distinguish between PD and CG with FS. It provides an approach to integrate FS as

  15. Detrended Fluctuation Analysis and Adaptive Fractal Analysis of Stride Time Data in Parkinson's Disease: Stitching Together Short Gait Trials

    PubMed Central

    Liebherr, Magnus; Haas, Christian T.

    2014-01-01

    Variability indicates motor control disturbances and is suitable to identify gait pathologies. It can be quantified by linear parameters (amplitude estimators) and more sophisticated nonlinear methods (structural information). Detrended Fluctuation Analysis (DFA) is one method to measure structural information, e.g., from stride time series. Recently, an improved method, Adaptive Fractal Analysis (AFA), has been proposed. This method has not been applied to gait data before. Fractal scaling methods (FS) require long stride-to-stride data to obtain valid results. However, in clinical studies, it is not usual to measure a large number of strides (e.g., strides). Amongst others, clinical gait analysis is limited due to short walkways, thus, FS seem to be inapplicable. The purpose of the present study was to evaluate FS under clinical conditions. Stride time data of five self-paced walking trials ( strides each) of subjects with PD and a healthy control group (CG) was measured. To generate longer time series, stride time sequences were stitched together. The coefficient of variation (CV), fractal scaling exponents (DFA) and (AFA) were calculated. Two surrogate tests were performed: A) the whole time series was randomly shuffled; B) the single trials were randomly shuffled separately and afterwards stitched together. CV did not discriminate between PD and CG. However, significant differences between PD and CG were found concerning and . Surrogate version B yielded a higher mean squared error and empirical quantiles than version A. Hence, we conclude that the stitching procedure creates an artificial structure resulting in an overestimation of true . The method of stitching together sections of gait seems to be appropriate in order to distinguish between PD and CG with FS. It provides an approach to integrate FS as standard in clinical gait analysis and to overcome limitations such as short walkways. PMID:24465708

  16. A Follow up Randomized Controlled Trial of "Time to Read": A Volunteer Mentoring Program

    ERIC Educational Resources Information Center

    Miller, Sarah; Connolly, Paul; Maguire, Lisa K.

    2011-01-01

    "Time to Read" is a volunteer mentoring program that recruits volunteers from the local business community to spend one hour of company time each week working on a one-to-one basis with primary school children aged 8 to 9 years with the aim of improving reading skills. The authors first evaluated the program in 2006-8 using a randomized controlled…

  17. A Phase III Randomized Trial of the Timing of Meloxicam With Iodine-125 Prostate Brachytherapy

    SciTech Connect

    Crook, Juanita; Patil, Nikhilesh; Wallace, Kris; Borg, Jette; Zhou, David; Ma, Clement; Pond, Greg

    2010-06-01

    Purpose: Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. Methods and Materials: From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. Results: Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. Conclusions: Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization.

  18. Reducing office workers’ sitting time: rationale and study design for the Stand Up Victoria cluster randomized trial

    PubMed Central

    2013-01-01

    Background Excessive time spent in sedentary behaviours (sitting or lying with low energy expenditure) is associated with an increased risk for type 2 diabetes, cardiovascular disease and some cancers. Desk-based office workers typically accumulate high amounts of daily sitting time, often in prolonged unbroken bouts. The Stand Up Victoria study aims to determine whether a 3-month multi-component intervention in the office setting reduces workplace sitting, particularly prolonged, unbroken sitting time, and results in improvements in cardio-metabolic biomarkers and work-related outcomes, compared to usual practice. Methods/Design A two-arm cluster-randomized controlled trial (RCT), with worksites as the unit of randomization, will be conducted in 16 worksites located in Victoria, Australia. Work units from one organisation (Department of Human Services, Australian Government) will be allocated to either the multi-component intervention (organisational, environmental [height-adjustable workstations], and individual behavioural strategies) or to a usual practice control group. The recruitment target is 160 participants (office-based workers aged 18–65 years and working at least 0.6 full time equivalent) per arm. At each assessment (0- [baseline], 3- [post intervention], and 12-months [follow-up]), objective measurement via the activPAL3 activity monitor will be used to assess workplace: sitting time (primary outcome); prolonged sitting time (sitting time accrued in bouts of ≥30 minutes); standing time; sit-to-stand transitions; and, moving time. Additional outcomes assessed will include: non-workplace activity; cardio-metabolic biomarkers and health indicators (including fasting glucose, lipids and insulin; anthropometric measures; blood pressure; and, musculoskeletal symptoms); and, work-related outcomes (presenteeism, absenteeism, productivity, work performance). Incremental cost-effectiveness and identification of both workplace and individual

  19. Subacute dietary toxicities of dicrotophos and dieldrin in time-replicated trials with young ring-necked pheasants and mallards

    USGS Publications Warehouse

    Hill, E.F.; Lamb, D.W.; Kenaga, E.E.

    1982-01-01

    The dietary toxicities of (E)-phosphoric acid 3-(dimethylamino)-1-methyl-3-oxo-1-propenyl dimethyl ester (dicrotophos) and 3,4,5,6,9,9-hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-dimethanonaphth[2,3-b]oxirene (dieldrin) to 10-day-old ring-necked pheasants (Phasianus colchicus) and 5-day-old mallards (Anas platyrhynchos) were compared in five time-replicated trials. Toxicities were calculated as median lethal concentrations (LC50s) based on 5 days of ad libitum feeding on geometrically spaced concentrations of toxicant. The LC50s were more uniform for dieldrin than for dicrotophos with both species and more uniform for pheasants than for mallards with both compounds. The LC50s of dieldrin and dicrotophos averaged 59 [standard deviation (SD) = 4.4] and 45 ppm (SD = 5.0) for pheasants, and 156 (SD = 24.9) and 102 ppm (SD = 24.9) for mallards. Changes in LC50s between successive trials, although possibly haphazard, were nearly always in the same direction for both compounds with both species. Feeding rates at various concentrations of equivalent potency gave meaningful insight into the sensitivity and vulnerability of both species to these insecticides. Comparisons of 5 and 10-day-old mallards demonstrated the importance of age differences to interpretation of short-term subacute toxicity data. For example, at 5 days dicrotophos was 1.5 times more toxic than dieldrin, but at 10 days dieldrin was 2.6 times more toxic. These differences are explained.

  20. The effect of time on CPR and automated external defibrillator skills in the Public Access Defibrillation Trial

    PubMed Central

    Christenson, Jim; Nafziger, Sarah; Compton, Scott; Vijayaraghavan, Kris; Slater, Brian; Ledingham, Robert; Powell, Judy; McBurnie, Mary Ann

    2009-01-01

    Background The time to skill deterioration between primary training/retraining and further retraining in Cardiopulmonary resuscitation (CPR) and automated external defibrillation (AED) for lay-persons is unclear. The Public Access Defibrillation (PAD) Trial was a multi-center randomized controlled trial evaluating survival after CPR-only vs. CPR+AED delivered by onsite non-medical volunteer responders in out-of-hospital cardiac arrest. Aims This sub-study evaluated the relationship of time between primary training/retraining and further retraining on volunteer performance during pretest AED and CPR skill evaluation. Methods Volunteers at 1260 facilities in 24 North American regions underwent training/retraining according to facility randomization, which included an initial session and a refresher session at approximately 6 months. Before the next retraining, a CPR and AED skill test was completed for 2729 volunteers. Primary outcome for the study was assessment of global competence of CPR or AED performance (adequate vs not adequate) using Chi-square tests for trends by time interval (3, 6, 9, and 12 months). Confirmatory (GEE) logistic regression analysis, adjusted for site and potential confounders. Results The proportion of volunteers judged to be competent did not diminish by interval (3,6,9,12 months) for either CPR or AED skills. After adjusting for site and potential confounders, longer intervals before to further retraining was associated with a slightly lower likelihood of performing adequate CPR but not with AED scores. Conclusions After primary training/retraining, the CPR skills of targeted lay responders deteriorate nominally but 80% remain competent up to one year. AED skills do not significantly deteriorate and 90% of volunteers remain competent up to one year. PMID:17303309

  1. The effects of mountain bike suspension systems on energy expenditure, physical exertion, and time trial performance during mountain bicycling.

    PubMed

    Seifert, J G; Luetkemeier, M J; Spencer, M K; Miller, D; Burke, E R

    1997-04-01

    The purpose of this 3-Phase study was to investigate the effects of suspension systems on muscular stress, energy expenditure, and time trial performance during mountain biking. Three suspension systems were tested, a rigid frame bike (RIG), a suspension fork bike (FS), and a front and rear suspension bike (FSR). Phase I and II consisted of cycling at 16.1 km.hr-1 over a flat, bumpy course for 63 min. Phase III consisted of ascending (ATT), descending (DTT), and cross country (XTT) time trials. Phase I assessed muscular stress by 24 h change in CK, Phase II assessed HR, VO2, VE, and Phase III assessed performance responses to the suspension systems. The 24 hr change in CK was greater for RIG than FS and FSR (+91.9 +/- 79.5 IU vs +8.6 +/- 17.5 IU and +9.7 +/- 21.8 IU). Mean HR was greater for RIG than FS and FSR (153.7 +/- 15.6 bpm vs 146.7 +/- 15.4 bpm, 146.3 +/- 16.2 bpm). Subjects rode significantly faster on FS than FSR and RIG during the XTT (30.9 +/- 2.0 min vs 32.3 +/- 3.6 min, 32.3 +/- 3.2 min). Subjects RPE was lower for FSR than FS and RIG, however, no differences were observed for VO2, VE, ATT, or DTT. Cyclists incurred less muscular stress, indicated by CK and HR, when riding the FS and FSR. Although the FS and FSR weigh from 0.7 to 2.2 kg more than RIG, no differences were observed for energy expenditure and that riding the FS in a XTT resulted in a faster finishing time than FSR or RIG.

  2. A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes)

    PubMed Central

    Biddle, Stuart J. H.; Edwardson, Charlotte L.; Wilmot, Emma G.; Yates, Thomas; Gorely, Trish; Bodicoat, Danielle H.; Ashra, Nuzhat; Khunti, Kamlesh; Nimmo, Myra A.; Davies, Melanie J.

    2015-01-01

    Aims 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. Methods 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. Results 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. Conclusions 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

  3. Effects of low and high cadence interval training on power output in flat and uphill cycling time-trials.

    PubMed

    Nimmerichter, Alfred; Eston, Roger; Bachl, Norbert; Williams, Craig

    2012-01-01

    This study tested the effects of low-cadence (60 rev min(-1)) uphill (Int(60)) or high-cadence (100 rev min(-1)) level-ground (Int(100)) interval training on power output (PO) during 20-min uphill (TT(up)) and flat (TT(flat)) time-trials. Eighteen male cyclists ([Formula: see text]: 58.6 ± 5.4 mL min(-1) kg(-1)) were randomly assigned to Int(60), Int(100) or a control group (Con). The interval training comprised two training sessions per week over 4 weeks, which consisted of six bouts of 5 min at the PO corresponding to the respiratory compensation point (RCP). For the control group, no interval training was conducted. A two-factor ANOVA revealed significant increases on performance measures obtained from a laboratory-graded exercise test (GXT) (P (max): 2.8 ± 3.0%; p < 0.01; PO and [Formula: see text] at RCP: 3.6 ± 6.3% and 4.7 ± 8.2%, respectively; p < 0.05; and [Formula: see text] at ventilatory threshold: 4.9 ± 5.6%; p < 0.01), with no significant group effects. Significant interactions between group and uphill and flat time-trial, pre- versus post-training on PO were observed (p < 0.05). Int(60) increased PO during both TT(up) (4.4 ± 5.3%) and TT(flat) (1.5 ± 4.5%). The changes were -1.3 ± 3.6, 2.6 ± 6.0% for Int(100) and 4.0 ± 4.6%, -3.5 ± 5.4% for Con during TT(up) and TT(flat), respectively. PO was significantly higher during TT(up) than TT(flat) (4.4 ± 6.0; 6.3 ± 5.6%; pre and post-training, respectively; p < 0.001). These findings suggest that higher forces during the low-cadence intervals are potentially beneficial to improve performance. In contrast to the GXT, the time-trials are ecologically valid to detect specific performance adaptations.

  4. Longitudinal Impact of a Family Critical Time Intervention on Children in High-Risk Families Experiencing Homelessness: A Randomized Trial.

    PubMed

    Shinn, Marybeth; Samuels, Judith; Fischer, Sean N; Thompkins, Amanda; Fowler, Patrick J

    2015-12-01

    A randomized trial compared effects of a Family Critical Time Intervention (FCTI) to usual care for children in 200 newly homeless families in which mothers had diagnosable mental illness or substance problems. Adapted from an evidence-based practice to prevent chronic homelessness for adults with mental illnesses, FCTI combines housing and structured, time-limited case management to connect families leaving shelter with community services. Families were followed at five time points over 24 months. Data on 311 children-99 ages 1.5-5 years, 113 ages 6-10 years, and 99 ages 11-16 years-included mother-, teacher-, and child-reports of mental health, school experiences, and psychosocial well-being. Analyses used hierarchical linear modeling to investigate intervention effects and changes in child functioning over time. Referral to FCTI reduced internalizing and externalizing problems in preschool-aged children and externalizing for adolescents 11-16. The intervention led to declines in self-reported school troubles for children 6-10 and 11-16. Both experimental and control children in all age groups showed reductions in symptoms over time. Although experimental results were scattered, they suggest that FCTI has the potential to improve mental health and school outcomes for children experiencing homelessness.

  5. The Microcomputer as Tachistoscope: Trials and Tribulations of Timing on the TRS-80.

    ERIC Educational Resources Information Center

    Mapou, Robert L.

    In this paper a hardware/software system is described which permits the use of the Radio Shack TRS-80 Model I as a tachistoscope in perceptual-cognitive research. Hardware requirements and configuration, problems in developing software routines to handle reaction and stimulus timing using the TRS-80, and the development of a routine for…

  6. Determination of optimal operation time for the management of acute cholecystitis: a clinical trial

    PubMed Central

    Ucar, Ahmet Deniz; Yakan, Savas; Carti, Erdem Baris; Coskun, Ali; Erkan, Nazif; Yildirim, Mehmet

    2014-01-01

    Introduction Although all studies have reported that laparoscopic cholecystectomy (LC) is a safe and effective treatment for acute cholecystitis, the optimal timing for the procedure is still the subject of some debate. Aim This retrospective analysis of a prospective database was aimed at comparing early with delayed LC for acute cholecystitis. Material and methods The LC was performed in 165 patients, of whom 83 were operated within 72 h of admission (group 1) and 82 patients after 72 h (group 2) with acute cholecystitis between January 2012 and August 2013. All data were collected prospectively and both groups compared in terms of age, sex, fever, white blood count count, ultrasound findings, operation time, conversion to open surgery, complications and mean hospital stay. Results The study included 165 patients, 53 men and 112 women, who had median age 54 (20–85) years. The overall conversion rate was 27.9%. There was no significant difference in conversion rates (21% vs. 34%) between groups (p = 0.08). The operation time (116 min vs. 102 min, p = 0.02) was significantly increased in group 1. The complication rates (9% vs. 18%, p = 0.03) and total hospital stay (3.8 days vs. 7.9 days, p = 0.001) were significantly reduced in group 1. Conclusions Early LC within 72 h of admission reduces complications and hospital stay and is the preferred approach for acute cholecystitis. PMID:25097711

  7. A logrank test-based method for sizing clinical trials with two co-primary time-to-event endpoints

    PubMed Central

    Sugimoto, Tomoyuki; Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R.

    2013-01-01

    We discuss sample size determination for clinical trials evaluating the joint effects of an intervention on two potentially correlated co-primary time-to-event endpoints. For illustration, we consider the most common case, a comparison of two randomized groups, and use typical copula families to model the bivariate endpoints. A correlation structure of the bivariate logrank statistic is specified to account for the correlation among the endpoints, although the between-group comparison is performed using the univariate logrank statistic. We propose methods to calculate the required sample size to compare the two groups and evaluate the performance of the methods and the behavior of required sample sizes via simulation. PMID:23307913

  8. Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials.

    PubMed

    Raza, Karim; Saber, Tajvur P; Kvien, Tore K; Tak, Paul P; Gerlag, Danielle M

    2012-12-01

    The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a 'window of opportunity' is now well established and considerable attention has been paid to when it might close. However, in order to study how long the window of opportunity lasts, the timing of its opening must be precisely defined. An analysis of definitions of 'onset' in clinical studies reveals imprecision and heterogeneity, making accurate assessment of this important concept of the 'window of opportunity' very difficult. In this paper we propose that, in clinical trials in early RA, data on durations since onset of symptoms and onset of joint swelling as well as disease duration based on fulfilment of classification criteria should be routinely presented.

  9. Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer

    PubMed Central

    Murray, Sonya R; Murchie, Peter; Campbell, Neil; Walter, Fiona M; Mazza, Danielle; Habgood, Emily; Kutzer, Yvonne; Martin, Andrew; Goodall, Stephen; Barnes, David J

    2015-01-01

    Introduction Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer. Methods/analysis The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms. Ethics and dissemination Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016. Trial

  10. Effect of Paralysis at the Time of ProSeal Laryngeal Mask Airway Insertion on Pharyngolaryngeal Morbidities. A Randomized Trial

    PubMed Central

    Shin, Hyun-Jung; Oh, Ah-Young; Park, Hee-Pyoung; Hwang, Jung-Won

    2015-01-01

    Neuromuscular block results in the loss of muscular tone in the upper airway, which might contribute to the increased postoperative airway morbidity followed by ProSeal laryngeal mask airway (PLMA) insertion. We compared the pharyngolaryngeal discomfort exerted by the PLMA according to the neuromuscular block. One hundred sixty patients undergoing surgery for breast disease or inguinal hernia were anesthetized with propofol and remifentanil by target controlled infusion. Rocuronium 0.6 mg/kg (NMBA group, n = 80) or normal saline (No-NMBA group, n = 80) was administered after the loss of consciousness, and one anesthesiologist inserted the PLMA. Postoperative pharyngolaryngeal discomfort was evaluated at postoperative 1 h. Traumatic event was recorded based on the blood trace on the surface of the PLMA cuff. Insertion time, insertion attempt number, sealing pressure, and fiberoptic brochoscopic grades were evaluated. Patients’ characteristics and the PLMA insertion condition (insertion time, successful insertion attempt number, fiberoptic bronchoscopic grade, and sealing pressure) were similar between the two groups. The PLMA can be successfully inserted in non-paralyzed patients with less postoperative pharyngolaryngeal discomfort than when a neuromuscular blocking agent is used (13.8% vs. 30.0%, P = 0.021). The incidence of traumatic events is also reduced when no neuromuscular blocking agent is used (16.3% vs. 32.5%, P = 0.026). Regardless of whether or not a surgical procedure requires muscular relaxation, there is no need to administer neuromuscular blocking agents solely for the purpose of PLMA insertion. Trial Registration ClinicalTrials.gov NCT01035021 PMID:26252522

  11. Reproducibility of a laboratory-based 40-km cycle time-trial on a stationary wind-trainer in highly trained cyclists.

    PubMed

    Laursen, P B; Shing, C M; Jenkins, D G

    2003-10-01

    The purpose of the present study was to examine the reproducibility of laboratory-based 40-km cycle time-trial performance on a stationary wind-trainer. Each week, for three consecutive weeks, and on different days, forty-three highly trained male cyclists (x +/- SD; age = 25 +/- 6 y; mass = 75 +/- 7 kg; peak oxygen uptake [VO (2)peak] = 64.8 +/- 5.2 ml x kg (-1) x min (-1)) performed: 1) a VO (2)peak test, and 2) a 40-km time-trial on their own racing bicycle mounted to a stationary wind-trainer (Cateye - Cyclosimulator). Data from all tests were compared using a one-way analysis of variance. Performance on the second and third 40-km time-trials were highly related (r = 0.96; p < 0.001), not significantly different (57 : 21 +/- 2 : 57 vs. 57 : 12 +/- 3 : 14 min:s), and displayed a low coefficient of variation (CV) = 0.9 +/- 0.7 %. Although the first 40-km time-trial (58 : 43 +/- 3 : 17 min:s) was not significantly different from the second and third tests (p = 0.06), inclusion of the first test in the assessment of reliability increased within-subject CV to 3.0 +/- 2.9 %. 40-km time-trial speed (km x h (-1)) was significantly (p < 0.001) related to peak power output (W; r = 0.75), VO (2)peak (l x min (-1); r = 0.53), and the second ventilatory turnpoint (l x min (-1); r = 0.68) measured during the progressive exercise tests. These data demonstrate that the assessment of 40-km cycle time-trial performance in well-trained endurance cyclists on a stationary wind-trainer is reproducible, provided the athletes perform a familiarization trial.

  12. Can Pacing Be Regulated by Post-Activation Potentiation? Insights from a Self-Paced 30 km Trial in Half-Marathon Runners

    PubMed Central

    Del Rosso, Sebastián; Barros, Edilberto; Tonello, Laís; Oliveira-Silva, Iransé; Behm, David G.; Foster, Carl; Boullosa, Daniel A.

    2016-01-01

    Purpose Given the co-existence of post-activation potentiation (PAP) and fatigue within muscle, it is not known whether PAP could influence performance and pacing during distance running by moderating fatigue. The aim of this study was to assess the influence of PAP on pacing, jumping and other physiological measures during a self-paced 30 km trial. Methods Eleven male endurance-trained runners (half-marathon runners) volunteered to participate in this study. Runners participated in a multi-stage 30 km trial. Before the trial started, determination of baseline blood lactate (bLa) and countermovement jump (CMJ) height was performed. The self-paced 30 km trial consisted of 6 × 5 km splits. At the end of each 5 km split (60 s break), data on time to complete the split, CMJ height, Rating of Perceived Exertion (RPE) and blood lactate were collected while heart rate was continuously monitored. Results There was a significant decrease in speed (e.g. positive pacing strategy after the 4th split, p<0.05) with a progressive increase in RPE throughout the trial. Compared with baseline, CMJ height was significantly (p<0.05) greater than baseline and was maintained until the end of the trial with an increase after the 5th split, concomitant with a significant reduction in speed and an increase in RPE. Significant correlations were found between ΔCMJ and ΔSPEED (r = 0.77 to 0.87, p<0.05) at different time points as well as between RPE and speed (r = -0.61 to -0.82, p<0.05). Conclusion Our results indicates that fatigue and potentiation co-exist during long lasting endurance events, and that the observed increase in jump performance towards the end of the trial could be reflecting a greater potentiation potentially perhaps counteracting the effects of fatigue and preventing further reductions in speed. PMID:26934357

  13. First Trial of Real-time Poloidal Beta Control in KSTAR

    NASA Astrophysics Data System (ADS)

    Han, Hyunsun; Hahn, S. H.; Bak, J. G.; Walker, M. L.; Woo, M. H.; Kim, J. S.; Kim, Y. J.; Bae, Y. S.; KSTAR Team

    2014-10-01

    Sustaining the plasma in a stable and a high performance condition is one of the important control issues for future steady state tokamaks. In the 2014 KSTAR campaign, we have developed a real-time poloidal beta (βp) control technique and carried out preliminary experiments to identify its feasibility. In the control system, the βp is calculated in real time using the measured diamagnetic loop signal (DLM03) with coil pickup corrections, and compared with the target value leading to the change of the neutral beam (NB) heating power using a feedback PID control algorithm. To match the required power of NB which is operated with constant voltage, the duty cycles of the modulation were adjusted as the ratio of the required power to the maximum achievable one. This paper will present the overall procedures of the βp control, the βp estimation process implemented in the plasma control system, and the analysis on the preliminary experimental results. This work is supported by the KSTAR research project funded by the Ministry of Science, ICT & Future Planning of Korea.

  14. Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome.

    PubMed

    Wright, Rachel L

    2015-01-01

    In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short-duration track cycling events is proposed to utilize an "all-out" strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para-cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times

  15. Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome

    PubMed Central

    Wright, Rachel L.

    2016-01-01

    In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short-duration track cycling events is proposed to utilize an “all-out” strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para-cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times

  16. Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome.

    PubMed

    Wright, Rachel L

    2015-01-01

    In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short-duration track cycling events is proposed to utilize an "all-out" strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para-cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times

  17. Experiential Virtual Scenarios With Real-Time Monitoring (Interreality) for the Management of Psychological Stress: A Block Randomized Controlled Trial

    PubMed Central

    Pallavicini, Federica; Morganti, Luca; Serino, Silvia; Scaratti, Chiara; Briguglio, Marilena; Crifaci, Giulia; Vetrano, Noemi; Giulintano, Annunziata; Bernava, Giuseppe; Tartarisco, Gennaro; Pioggia, Giovanni; Raspelli, Simona; Cipresso, Pietro; Vigna, Cinzia; Grassi, Alessandra; Baruffi, Margherita; Wiederhold, Brenda; Riva, Giuseppe

    2014-01-01

    Background The recent convergence between technology and medicine is offering innovative methods and tools for behavioral health care. Among these, an emerging approach is the use of virtual reality (VR) within exposure-based protocols for anxiety disorders, and in particular posttraumatic stress disorder. However, no systematically tested VR protocols are available for the management of psychological stress. Objective Our goal was to evaluate the efficacy of a new technological paradigm, Interreality, for the management and prevention of psychological stress. The main feature of Interreality is a twofold link between the virtual and the real world achieved through experiential virtual scenarios (fully controlled by the therapist, used to learn coping skills and improve self-efficacy) with real-time monitoring and support (identifying critical situations and assessing clinical change) using advanced technologies (virtual worlds, wearable biosensors, and smartphones). Methods The study was designed as a block randomized controlled trial involving 121 participants recruited from two different worker populations—teachers and nurses—that are highly exposed to psychological stress. Participants were a sample of teachers recruited in Milan (Block 1: n=61) and a sample of nurses recruited in Messina, Italy (Block 2: n=60). Participants within each block were randomly assigned to the (1) Experimental Group (EG): n=40; B1=20, B2=20, which received a 5-week treatment based on the Interreality paradigm; (2) Control Group (CG): n=42; B1=22, B2=20, which received a 5-week traditional stress management training based on cognitive behavioral therapy (CBT); and (3) the Wait-List group (WL): n=39, B1=19, B2=20, which was reassessed and compared with the two other groups 5 weeks after the initial evaluation. Results Although both treatments were able to significantly reduce perceived stress better than WL, only EG participants reported a significant reduction (EG=12% vs CG=0

  18. Stress and Fatigue Management Using Balneotherapy in a Short-Time Randomized Controlled Trial.

    PubMed

    Rapolienė, Lolita; Razbadauskas, Artūras; Sąlyga, Jonas; Martinkėnas, Arvydas

    2016-01-01

    Objective. To investigate the influence of high-salinity geothermal mineral water on stress and fatigue. Method. 180 seamen were randomized into three groups: geothermal (65), music (50), and control (65). The geothermal group was administered 108 g/L salinity geothermal water bath for 2 weeks five times a week. Primary outcome was effect on stress and fatigue. Secondary outcomes were the effect on cognitive function, mood, and pain. Results. The improvements after balneotherapy were a reduction in the number and intensity of stress-related symptoms, a reduction in pain and general, physical, and mental fatigue, and an improvement in stress-related symptoms management, mood, activation, motivation, and cognitive functions with effect size from 0.8 to 2.3. In the music therapy group, there were significant positive changes in the number of stress symptoms, intensity, mood, pain, and activity with the effect size of 0.4 to 1.1. The researchers did not observe any significant positive changes in the control group. The comparison between the groups showed that balneotherapy was superior to music therapy and no treatment group. Conclusions. Balneotherapy is beneficial for stress and fatigue reduction in comparison with music or no therapy group. Geothermal water baths have a potential as an efficient approach to diminish stress caused by working or living conditions. PMID:27051455

  19. Stress and Fatigue Management Using Balneotherapy in a Short-Time Randomized Controlled Trial

    PubMed Central

    Razbadauskas, Artūras; Sąlyga, Jonas; Martinkėnas, Arvydas

    2016-01-01

    Objective. To investigate the influence of high-salinity geothermal mineral water on stress and fatigue. Method. 180 seamen were randomized into three groups: geothermal (65), music (50), and control (65). The geothermal group was administered 108 g/L salinity geothermal water bath for 2 weeks five times a week. Primary outcome was effect on stress and fatigue. Secondary outcomes were the effect on cognitive function, mood, and pain. Results. The improvements after balneotherapy were a reduction in the number and intensity of stress-related symptoms, a reduction in pain and general, physical, and mental fatigue, and an improvement in stress-related symptoms management, mood, activation, motivation, and cognitive functions with effect size from 0.8 to 2.3. In the music therapy group, there were significant positive changes in the number of stress symptoms, intensity, mood, pain, and activity with the effect size of 0.4 to 1.1. The researchers did not observe any significant positive changes in the control group. The comparison between the groups showed that balneotherapy was superior to music therapy and no treatment group. Conclusions. Balneotherapy is beneficial for stress and fatigue reduction in comparison with music or no therapy group. Geothermal water baths have a potential as an efficient approach to diminish stress caused by working or living conditions. PMID:27051455

  20. Dairy-based preexercise meal does not affect gut comfort or time-trial performance in female cyclists.

    PubMed

    Haakonssen, Eric C; Ross, Megan L; Cato, Louise E; Nana, Alisa; Knight, Emma J; Jenkins, David G; Martin, David T; Burke, Louise M

    2014-10-01

    Some athletes avoid dairy in the meal consumed before exercise due to fears about gastrointestinal discomfort. Regular exclusion of dairy foods may unnecessarily reduce intake of high quality proteins and calcium with possible implications for body composition and bone health. This study compared the effects of meals that included (Dairy) or excluded (Control) dairy foods on gastric comfort and subsequent cycling performance. Well-trained female cyclists (n = 32; mean ± SD; 24.3 ± 4.1 y; VO(2peak) 57.1 ± 4.9 ml/kg/min) completed two trials (randomized cross-over design) in which they consumed a meal (2 g/kg carbohydrate and 54 kJ/kg) 2 hr before a 90-min cycle session (80 min at 60% maximal aerobic power followed by a 10-min time trial; TT). The dairy meal contained 3 servings of dairy foods providing ~1350 mg calcium. Gut comfort and palatability were measured using questionnaires. Performance was measured as maximum mean power during the TT (MMP10(min)). There was no statistical or clinical evidence of an effect of meal type on MMP10(min) with a mean difference (Dairy - Control) of 4 W (95% CI [-2, 9]). There was no evidence of an association between pretrial gut comfort and meal type (p = .15) or between gut comfort delta scores and meal type postmeal (p = .31), preexercise (p = .17) or postexercise (p = .80). There was no statistical or clinical evidence of a difference in palatability between meal types. In summary, substantial amounts of dairy foods can be included in meals consumed before strenuous cycling without impairing either gut comfort or performance.

  1. Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial

    PubMed Central

    Mikkelsen, Torben S.; Sparreboom, Alex; Cheng, Cheng; Zhou, Yinmei; Boyett, James M.; Raimondi, Susana C.; Panetta, John C.; Bowman, W. Paul; Sandlund, John T.; Pui, Ching-Hon; Relling, Mary V.; Evans, William E.

    2011-01-01

    Purpose To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes. Methods From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7 in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells). Results The 24-hour infusion resulted in significantly higher amounts of MTXPG1-7 in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109 cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7 accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109 cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7 but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7 accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation. Conclusion Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes. PMID:21444869

  2. Randomized Trial of Psychological Interventions to Preventing Postpartum Depression among Iranian First-time Mothers

    PubMed Central

    Fathi-Ashtiani, Ali; Ahmadi, Ahmad; Ghobari-Bonab, Bagher; Azizi, Mohammed Parsa; Saheb-Alzamani, Sayeh Moosavi

    2015-01-01

    Background: The current study was conducted to examine the effect of cognitive behavior therapy on the reduction postpartum mood disorder and increasing the self-esteem of at-risk Iranian mothers. Methods: In this quasi-experimental study, 135 at-risk mothers were selected from the population by means of cluster sampling and randomly assigned into one of two groups: Intervention (n = 64), or control (n = 71). The control group received usual medical care, and the intervention group received an eight sessions’ cognitive behavior program during pregnancy. Assessments were administered at two time points (pretest at the beginning of the third trimester and posttest at 2 weeks postpartum). Beck anxiety, beck depression, Edinburgh postpartum depression, (PPD) Coopersmith self-esteem, and religious attitude questionnaire were used to collect data. Results: The mean age of participants was 25.8 ± 3.7 years. One-third of them had either bachelor or higher degrees in education (33%). About two-third of participants were unemployment with similar distribution in both the groups (intervention = 80%, control = 83%). The majority (70%) of the participants had cesarean section deliveries. There were no statistically significant differences respects to sociodemographic characteristics between the control and intervention groups (P > 0.05). The multivariate analysis of covariance results showed that the average scores of PPD were reduced significantly in the intervention group (P < 0.001). Also while the mean score of anxiety in the intervention group decreased from 23.31 (standard error [SE] =12.11) to 16.64 (SE = 8.33) and self-esteem increased from 29.09 (SE = 3.51) to 31.81 (SE = 2.76), no change was statistically significant in comparison to the control group. Conclusions: According to the findings of the present study, cognitive behavior intervention is effective in reducing PPD in at-risk mothers. PMID:26682030

  3. Early biomarker activity in severe sepsis and septic shock and a contemporary review of immunotherapy trials: not a time to give up, but to give it earlier.

    PubMed

    Rivers, Emanuel P; Jaehne, Anja Kathrin; Nguyen, H Bryant; Papamatheakis, Demosthenes G; Singer, Daniel; Yang, James J; Brown, Samantha; Klausner, Howard

    2013-02-01

    Improving time to diagnosis and intervention has positively impacted outcomes in acute myocardial infarction, stroke, and trauma through elucidating the early pathogenesis of those diseases. This insight may partly explain the futility of time-insensitive immunotherapy trials for severe sepsis and septic shock. The aim of this study was to examine the early natural history of circulatory biomarker activity in sepsis, relative to previous animal and human outcome trials. We conducted a literature search using PubMed, MEDLINE, and Google Scholar to identify outcome trials targeting biomarkers with emphasis on the timing of therapy. These findings were compared with the biomarker activity observed over the first 72 h of hospital presentation in a cohort of severe sepsis and septic shock patients. Biomarker levels in animal and human research models are elevated within 30 min after exposure to an inflammatory septic stimulus. Consistent with these findings, the biomarker cascade is activated at the most proximal point of hospital presentation in our patient cohort. These circulatory biomarkers overlap; some have bimodal patterns and generally peak between 3 and 36 h while diminishing over the subsequent 72 h of observation. When this is taken into account, prior outcome immunotherapy trials have generally enrolled patients after peak circulatory biomarker concentrations. In previous immunotherapy sepsis trials, intervention was delayed after the optimal window of peak biomarker activity. As a result, future studies need to recalibrate the timing of enrollment and administration of immunotherapy agents that still may hold great promise for this deadly disease.

  4. A Sucrose Mouth Rinse Does Not Improve 1-hr Cycle Time Trial Performance When Performed in the Fasted or Fed State.

    PubMed

    Trommelen, Jorn; Beelen, Milou; Mullers, Marjan; Gibala, Martin J; van Loon, Luc J C; Cermak, Naomi M

    2015-12-01

    Carbohydrate mouth rinsing during exercise has been suggested to enhance performance of short (45-60 min) bouts of high-intensity (>75% VO2peak) exercise. Recent studies indicate that this performance enhancing effect may be dependent on the prandial state of the athlete. The purpose of this study was to define the impact of a carbohydrate mouth rinse on ~1-hr time trial performance in both the fasted and fed states. Using a double-blind, crossover design, 14 trained male cyclists (27 ± 6 years; 5.0 ± 0.5 W · kg(-1)) were selected to perform 4 time trials of ~1 hr (1,032 ± 127 kJ) on a cycle ergometer while rinsing their mouths with a 6.4% sucrose solution (SUC) or a noncaloric sweetened placebo (PLA) for 5 s at the start and at every 12.5% of their set amount of work completed. Two trials were performed in an overnight fasted state and two trials were performed 2 h after consuming a standardized breakfast. Performance time did not differ between any of the trials (fasted-PLA: 68.6 ± 7.2; fasted-SUC: 69.6 ± 7.5; fed-PLA: 67.6 ± 6.6; and fed-SUC: 69.0 ± 6.3 min; Prandial State × Mouth Rinse Solution p = .839; main effect prandial state p = .095; main effect mouth rinse solution p = .277). In line, mean power output and heart rate during exercise did not differ between trials. In conclusion, a sucrose mouth rinse does not improve ~1-hr time trial performance in well-trained cyclists when performed in either the fasted or the fed state.

  5. The feasibility, time savings and economic impact of a designated time appointment system at a busy HIV care clinic in Kenya: a randomized controlled trial

    PubMed Central

    Kwena, Zachary A; Njoroge, Betty W; Cohen, Craig R; Oyaro, Patrick; Shikari, Rosemary; Kibaara, Charles K; Bukusi, Elizabeth A

    2015-01-01

    Introduction As efforts are made to reach universal access to ART in Kenya, the problem of congestion at HIV care clinics is likely to worsen. We evaluated the feasibility and the economic benefits of a designated time appointment system as a solution to decongest HIV care clinics. Methods This was an explanatory two-arm open-label randomized controlled trial that enrolled 354 consenting participants during their normal clinic days and followed-up at subsequent clinic appointments for up to nine months. Intervention arm participants were given specific dates and times to arrive at the clinic for their next appointment while those in the control arm were only given the date and had the discretion to decide on the time to arrive as is the standard practice. At follow-up visits, we recorded arrival and departure times and asked the monetary value of work participants engaged in before and after clinic. We conducted multiple imputation to replace missing data in our primary outcome variables to allow for intention-to-treat analysis; and analyzed the data using Mann–Whitney U test. Results Overall, 72.1% of the intervention participants arrived on time, 13.3% arrived ahead of time and 14.6% arrived past scheduled time. Intervention arm participants spent a median of 65 [interquartile range (IQR), 52–87] minutes at the clinic compared to 197 (IQR, 173–225) minutes for control participants (p<0.01). Furthermore, intervention arm participants were more productively engaged on their clinic days valuing their cumulative work at a median of USD 10.5 (IQR, 60.0–16.8) compared to participants enrolled in the control arm who valued their work at USD 8.3 (IQR, 5.5–12.9; p=0.02). Conclusions A designated time appointment system is feasible and provides substantial time savings associated with greater economic productivity for HIV patients attending a busy HIV care clinic. PMID:26163505

  6. Tracking real-time neural activation of conceptual knowledge using single-trial event-related potentials.

    PubMed

    Amsel, Ben D

    2011-04-01

    Empirically derived semantic feature norms categorized into different types of knowledge (e.g., visual, functional, auditory) can be summed to create number-of-feature counts per knowledge type. Initial evidence suggests several such knowledge types may be recruited during language comprehension. The present study provides a more detailed understanding of the timecourse and intensity of influence of several such knowledge types on real-time neural activity. A linear mixed-effects model was applied to single trial event-related potentials for 207 visually presented concrete words measured on total number of features (semantic richness), imageability, and number of visual motion, color, visual form, smell, taste, sound, and function features. Significant influences of multiple feature types occurred before 200ms, suggesting parallel neural computation of word form and conceptual knowledge during language comprehension. Function and visual motion features most prominently influenced neural activity, underscoring the importance of action-related knowledge in computing word meaning. The dynamic time courses and topographies of these effects are most consistent with a flexible conceptual system wherein temporally dynamic recruitment of representations in modal and supramodal cortex are a crucial element of the constellation of processes constituting word meaning computation in the brain.

  7. Metabolic consequences of β-alanine supplementation during exhaustive supramaximal cycling and 4000-m time-trial performance.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-08-01

    The present study investigated the effects of β-alanine supplementation on the resultant blood acidosis, lactate accumulation, and energy provision during supramaximal-intensity cycling, as well as the aerobic and anaerobic contribution to power output during a 4000-m cycling time trial (TT). Seventeen trained cyclists (maximal oxygen uptake = 4.47 ± 0.55 L·min(-1)) were administered 6.4 g of β-alanine (n = 9) or placebo (n = 8) daily for 4 weeks. Participants performed a supramaximal cycling test to exhaustion (equivalent to 120% maximal oxygen uptake) before (PreExh) and after (PostExh) the 4-week supplementation period, as well as an additional postsupplementation supramaximal cycling test identical in duration and power output to PreExh (PostMatch). Anaerobic capacity was quantified and blood pH, lactate, and bicarbonate concentrations were measured pre-, immediately post-, and 5 min postexercise. Subjects also performed a 4000-m cycling TT before and after supplementation while the aerobic and anaerobic contributions to power output were quantified. β-Alanine supplementation increased time to exhaustion (+12.8 ± 8.2 s; P = 0.041) and anaerobic capacity (+1.1 ± 0.7 kJ; P = 0.048) in PostExh compared with PreExh. Performance time in the 4000-m TT was reduced following β-alanine supplementation (-6.3 ± 4.6 s; P = 0.034) and the mean anaerobic power output was likely to be greater (+6.2 ± 4.5 W; P = 0.035). β-Alanine supplementation increased time to exhaustion concomitant with an augmented anaerobic capacity during supramaximal intensity cycling, which was also mirrored by a meaningful increase in the anaerobic contribution to power output during a 4000-m cycling TT, resulting in an enhanced overall performance. PMID:27467218

  8. Metabolic consequences of β-alanine supplementation during exhaustive supramaximal cycling and 4000-m time-trial performance.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-08-01

    The present study investigated the effects of β-alanine supplementation on the resultant blood acidosis, lactate accumulation, and energy provision during supramaximal-intensity cycling, as well as the aerobic and anaerobic contribution to power output during a 4000-m cycling time trial (TT). Seventeen trained cyclists (maximal oxygen uptake = 4.47 ± 0.55 L·min(-1)) were administered 6.4 g of β-alanine (n = 9) or placebo (n = 8) daily for 4 weeks. Participants performed a supramaximal cycling test to exhaustion (equivalent to 120% maximal oxygen uptake) before (PreExh) and after (PostExh) the 4-week supplementation period, as well as an additional postsupplementation supramaximal cycling test identical in duration and power output to PreExh (PostMatch). Anaerobic capacity was quantified and blood pH, lactate, and bicarbonate concentrations were measured pre-, immediately post-, and 5 min postexercise. Subjects also performed a 4000-m cycling TT before and after supplementation while the aerobic and anaerobic contributions to power output were quantified. β-Alanine supplementation increased time to exhaustion (+12.8 ± 8.2 s; P = 0.041) and anaerobic capacity (+1.1 ± 0.7 kJ; P = 0.048) in PostExh compared with PreExh. Performance time in the 4000-m TT was reduced following β-alanine supplementation (-6.3 ± 4.6 s; P = 0.034) and the mean anaerobic power output was likely to be greater (+6.2 ± 4.5 W; P = 0.035). β-Alanine supplementation increased time to exhaustion concomitant with an augmented anaerobic capacity during supramaximal intensity cycling, which was also mirrored by a meaningful increase in the anaerobic contribution to power output during a 4000-m cycling TT, resulting in an enhanced overall performance.

  9. Optimal power-to-mass ratios when predicting flat and hill-climbing time-trial cycling.

    PubMed

    Nevill, A M; Jobson, S A; Davison, R C R; Jeukendrup, A E

    2006-07-01

    The purpose of this article was to establish whether previously reported oxygen-to-mass ratios, used to predict flat and hill-climbing cycling performance, extend to similar power-to-mass ratios incorporating other, often quick and convenient measures of power output recorded in the laboratory [maximum aerobic power (W(MAP)), power output at ventilatory threshold (W(VT)) and average power output (W(AVG)) maintained during a 1 h performance test]. A proportional allometric model was used to predict the optimal power-to-mass ratios associated with cycling speeds during flat and hill-climbing cycling. The optimal models predicting flat time-trial cycling speeds were found to be (W(MAP)m(-0.48))(0.54), (W(VT)m(-0.48))(0.46) and (W(AVG)m(-0.34))(0.58) that explained 69.3, 59.1 and 96.3% of the variance in cycling speeds, respectively. Cross-validation results suggest that, in conjunction with body mass, W(MAP) can provide an accurate and independent prediction of time-trial cycling, explaining 94.6% of the variance in cycling speeds with the standard deviation about the regression line, s=0.686 km h(-1). Based on these models, there is evidence to support that previously reported VO2-to-mass ratios associated with flat cycling speed extend to other laboratory-recorded measures of power output (i.e. Wm(-0.32)). However, the power-function exponents (0.54, 0.46 and 0.58) would appear to conflict with the assumption that the cyclists' speeds should be proportional to the cube root (0.33) of power demand/expended, a finding that could be explained by other confounding variables such as bicycle geometry, tractional resistance and/or the presence of a tailwind. The models predicting 6 and 12% hill-climbing cycling speeds were found to be proportional to (W(MAP)m(-0.91))(0.66), revealing a mass exponent, 0.91, that also supports previous research.

  10. Decoding a bistable percept with integrated time-frequency representation of single-trial local field potential

    NASA Astrophysics Data System (ADS)

    Wang, Zhisong; Logothetis, Nikos K.; Liang, Hualou

    2008-12-01

    Bistable perception emerges when a stimulus under continuous view is perceived as the alternation of two mutually exclusive states. Such a stimulus provides a unique opportunity for understanding the neural basis of visual perception because it dissociates the perception from the visual input. In this paper we analyze the dynamic activity of local field potential (LFP), simultaneously collected from multiple channels in the middle temporal (MT) visual cortex of a macaque monkey, for decoding its bistable structure-from-motion (SFM) perception. Based on the observation that the discriminative information of neuronal population activity evolves and accumulates over time, we propose to select features from the integrated time-frequency representation of LFP using a relaxation (RELAX) algorithm and a sequential forward selection (SFS) algorithm with maximizing the Mahalanobis distance as the criterion function. The integrated-spectrogram based feature selection is much more robust and can achieve significantly better features than the instantaneous-spectrogram based feature selection. We exploit the support vector machines (SVM) classifier and the linear discriminant analysis (LDA) classifier based on the selected features to decode the reported perception on a single trial basis. Our results demonstrate the excellent performance of the integrated-spectrogram based feature selection and suggest that the features in the gamma frequency band (30-100 Hz) of LFP within specific temporal windows carry the most discriminative information for decoding bistable perception. The proposed integrated-spectrogram based feature selection approach may have potential for a myriad of applications involving multivariable time series such as brain-computer interfaces (BCI).

  11. Preconception Low Dose Aspirin and Time to Pregnancy: Findings From the Effects of Aspirin in Gestation and Reproduction Randomized Trial

    PubMed Central

    Mumford, Sunni L.; Schliep, Karen C.; Sjaarda, Lindsey A.; Stanford, Joseph B.; Lesher, Laurie L.; Wactawski-Wende, Jean; Lynch, Anne M.; Townsend, Janet M.; Perkins, Neil J.; Zarek, Shvetha M.; Tsai, Michael Y.; Chen, Zhen; Faraggi, David; Galai, Noya; Silver, Robert M.

    2015-01-01

    Objective: The objective was to determine the effect of preconception-initiated daily low-dose aspirin (LDA; 81 mg/day) treatment on time to pregnancy in women with a history of pregnancy loss. Design: This was a multicenter, block-randomized, double-blind, placebo-controlled trial. Participants were block-randomized by center and eligibility stratum. Setting: The study was conducted at four U.S.A. medical centers (2007–2012). Participants: Participants women aged 18–40 years actively attempting pregnancy, stratified by eligibility criteria: the “original” stratum, women with one loss <20 weeks' gestation during the previous year; and the “expanded” stratum, women with one or two previous losses of any gestational age regardless of time since loss. Intervention: Daily LDA was compared with matching placebo for up to six menstrual cycles of attempting pregnancy. Main Outcome Measure: Time to hCG detected pregnancy and clinically confirmed pregnancy, analyzed by intention-to-treat, was measured. Results: Of the 1228 women randomly assigned to LDA (n = 615) or placebo (n = 613), 410 (67%) women receiving LDA achieved pregnancy compared to 382 (63%) receiving placebo, corresponding to a fecundability odds ratio (FOR) of 1.14 (95% CI: 0.97, 1.33). Among women in the original stratum (n = 541), LDA was associated with increased fecundability compared to placebo (FOR: 1.28; 95%CI: 1.02, 1.62). Conclusions: Preconception-initiated LDA treatment resulted in a nonsignificant increase in fecundability of 14% in women with a history of 1–2 pregnancy losses, and a significant increase of 28% in women with a history of only one pregnancy loss of <20 weeks' gestation in the preceding year. Preconception-initiated LDA may increase fecundability in certain women with a recent early pregnancy loss. PMID:25710565

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

    PubMed Central

    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

  13. Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

    NASA Astrophysics Data System (ADS)

    Rodrigues, Pedro L.; Moreira, António H. J.; Rodrigues, Nuno F.; Pinho, A. C. M.; Fonseca, Jaime C.; Lima, Estevão.; Vilaça, João. L.

    2014-03-01

    Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

  14. Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202

    PubMed Central

    Venuto, Charles S.; Mollan, Katie; Ma, Qing; Daar, Eric S.; Sax, Paul E.; Fischl, Margaret; Collier, Ann C.; Smith, Kimberly Y.; Tierney, Camlin; Morse, Gene D.

    2014-01-01

    Objectives It is uncertain whether HIV-1 antiretroviral exposure and clinical response varies between males and females or different race/ethnic groups. We describe ritonavir-enhanced atazanavir pharmacokinetics in relation to virological failure, safety and tolerability in treatment-naive individuals to investigate potential differences. Methods Plasma samples were collected from participants in AIDS Clinical Trials Group Study A5202 for measurement of antiretroviral concentrations. Individual estimates of apparent oral clearance of atazanavir (L/h) were calculated from a one-compartment model and divided into tertiles as slow (<7), middle (7 to <9; reference group) and fast (≥9). Associations between atazanavir clearance and clinical outcomes were estimated with a hazard ratio (HR) from Cox proportional hazards models. Interactions between atazanavir clearance and sex, race/ethnicity and NRTIs were investigated for each of the outcomes. Results Among 786 participants, average atazanavir clearance was slower in females (n = 131) than males (n = 655). Atazanavir clearance was associated with time to virological failure (P = 0.053) and this relationship differed significantly by sex (P = 0.003). Females in the fast atazanavir clearance group had shorter time to virological failure (HR 3.49; 95% CI 1.24–9.84) compared with the middle (reference) atazanavir clearance group. Among males, the slow atazanavir clearance group had a higher risk of virological failure (HR 2.10; 95% CI 1.16–3.77). Conclusions Atazanavir clearance differed by sex. Females with fast clearance and males with slow clearance had increased risk of virological failure. PMID:25159623

  15. Beyond the futility argument: the fair process approach and time-limited trials for managing dialysis conflict.

    PubMed

    Rinehart, Ann

    2013-11-01

    Futility is an ancient concept arising from Greek mythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician-patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association's clinical practice guideline Shared Decision-Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline. PMID:23868900

  16. Beyond the futility argument: the fair process approach and time-limited trials for managing dialysis conflict.

    PubMed

    Rinehart, Ann

    2013-11-01

    Futility is an ancient concept arising from Greek mythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician-patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association's clinical practice guideline Shared Decision-Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline.

  17. Effectiveness of behavioral graded activity after first-time lumbar disc surgery: short term results of a randomized controlled trial.

    PubMed

    Ostelo, R W J G; de Vet, H C W; Berfelo, M W; Kerckhoffs, M R; Vlaeyen, J W S; Wolters, P M J C; van den Brandt, P A

    2003-12-01

    Behavioral approaches to treating patients following lumbar disc surgery are becoming increasingly popular. The treatment method is based on the assumption that pain and pain disability are not only influenced by somatic pathology, if found, but also by psychological and social factors. A recent study highlighted the effectiveness of cognitive-behavioral interventions, as compared to no treatment, for chronic low back patients. However, to the authors' knowledge, there is no randomized controlled trial that evaluates a behavioral program for patients following lumbar disc surgery. The purpose of this study was to assess the effectiveness of a behavioral graded activity (BGA) program compared to usual care (UC) in physiotherapy following first-time lumbar disc surgery. The BGA program was a patient-tailored intervention based upon operant therapy. The essence of the BGA is to teach patients that it is safe to increase activity levels. The study was designed as a randomized controlled trial. Assessments were carried out before and after treatment by an observer blinded to treatment allocation. Patients suffering residual symptoms restricting their activities of daily living and/or work at the 6 weeks post-surgery consultation by the neurosurgeon were included. The exclusion criteria were: complications during surgery, any relevant underlying pathology, and any contraindication to physiotherapy or the BGA program. Primary outcome measures were the patient's Global Perceived Effect and the functional status. Secondary measures were: fear of movement, viewing pain as extremely threatening, pain, severity of the main complaint, range of motion, and relapses. Physiotherapists in the BGA group received proper training. Between November 1997 and December 1999, 105 patients were randomized; 53 into the UC group and 52 into the BGA group. The unadjusted analysis shows a 19.3% (95% CI: 0.1 to 38.5) statistically significant difference to the advantage of the UC group on Global

  18. A Randomized Controlled Trial to Evaluate the Benefits of a Multimedia Educational Program for First-Time Hearing Aid Users

    PubMed Central

    Brandreth, Marian; Brassington, William; Leighton, Paul; Wharrad, Heather

    2016-01-01

    Objectives: The aims of this study were to (1) develop a series of short interactive videos (or reusable learning objects [RLOs]) covering a broad range of practical and psychosocial issues relevant to the auditory rehabilitation for first-time hearing aid users; (2) establish the accessibility, take-up, acceptability and adherence of the RLOs; and (3) assess the benefits and cost-effectiveness of the RLOs. Design: The study was a single-center, prospective, randomized controlled trial with two arms. The intervention group (RLO+, n = 103) received the RLOs plus standard clinical service including hearing aid(s) and counseling, and the waitlist control group (RLO−, n = 100) received standard clinical service only. The effectiveness of the RLOs was assessed 6-weeks posthearing aid fitting. Seven RLOs (total duration 1 hr) were developed using a participatory, community of practice approach involving hearing aid users and audiologists. RLOs included video clips, illustrations, animations, photos, sounds and testimonials, and all were subtitled. RLOs were delivered through DVD for TV (50.6%) and PC (15.2%), or via the internet (32.9%). Results: RLO take-up was 78%. Adherence overall was at least 67%, and 97% in those who attended the 6-week follow-up. Half the participants watched the RLOs two or more times, suggesting self-management of their hearing loss, hearing aids, and communication. The RLOs were rated as highly useful and the majority of participants agreed the RLOs were enjoyable, improved their confidence and were preferable to written information. Postfitting, there was no significant between-group difference in the primary outcome measure, overall hearing aid use. However, there was significantly greater hearing aid use in the RLO+ group for suboptimal users. Furthermore, the RLO+ group had significantly better knowledge of practical and psychosocial issues, and significantly better practical hearing aid skills than the RLO− group. Conclusions: The RLOs

  19. Evaluation of the UP4FUN Intervention: A Cluster Randomized Trial to Reduce and Break Up Sitting Time in European 10-12-Year-Old Children

    PubMed Central

    Vik, Frøydis N.; Lien, Nanna; Berntsen, Sveinung; De Bourdeaudhuij, Ilse; Grillenberger, Monika; Manios, Yannis; Kovacs, Eva; Chinapaw, Mai J. M.; Brug, Johannes; Bere, Elling

    2015-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. Trial Registration International Standard Randomized Controlled Trial Number Registry ISRCTN34562078 PMID:25826704

  20. Harnessing Technology to Improve Clinical Trials: Study of Real-Time Informatics to Collect Data, Toxicities, Image Response Assessments, and Patient-Reported Outcomes in a Phase II Clinical Trial

    PubMed Central

    Pietanza, M. Catherine; Basch, Ethan M.; Lash, Alex; Schwartz, Lawrence H.; Ginsberg, Michelle S.; Zhao, Binsheng; Shouery, Marwan; Shaw, Mary; Rogak, Lauren J.; Wilson, Manda; Gabow, Aaron; Latif, Marcia; Lin, Kai-Hsiung; Wu, Qinfei; Kass, Samantha L.; Miller, Claire P.; Tyson, Leslie; Sumner, Dyana K.; Berkowitz-Hergianto, Alison; Sima, Camelia S.; Kris, Mark G.

    2013-01-01

    Purpose In clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. Patients and Methods We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured. Results Forty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. Conclusion Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions. PMID:23630218

  1. Effects of lowering body temperature via hyperhydration, with and without glycerol ingestion and practical precooling on cycling time trial performance in hot and humid conditions

    PubMed Central

    2012-01-01

    Background Hypohydration and hyperthermia are factors that may contribute to fatigue and impairment of endurance performance. The purpose of this study was to investigate the effectiveness of combining glycerol hyperhydration and an established precooling technique on cycling time trial performance in hot environmental conditions. Methods Twelve well-trained male cyclists performed three 46.4-km laboratory-based cycling trials that included two climbs, under hot and humid environmental conditions (33.3 ± 1.1°C; 50 ± 6% r.h.). Subjects were required to hyperhydrate with 25 g.kg-1 body mass (BM) of a 4°C beverage containing 6% carbohydrate (CON) 2.5 h prior to the time trial. On two occasions, subjects were also exposed to an established precooling technique (PC) 60 min prior to the time trial, involving 14 g.kg-1 BM ice slurry ingestion and applied iced towels over 30 min. During one PC trial, 1.2 g.kg-1 BM glycerol was added to the hyperhydration beverage in a double-blind fashion (PC+G). Statistics used in this study involve the combination of traditional probability statistics and a magnitude-based inference approach. Results Hyperhydration resulted in large reductions (−0.6 to −0.7°C) in rectal temperature. The addition of glycerol to this solution also lowered urine output (330 ml, 10%). Precooling induced further small (−0.3°C) to moderate (−0.4°C) reductions in rectal temperature with PC and PC+G treatments, respectively, when compared with CON (0.0°C, P<0.05). Overall, PC+G failed to achieve a clear change in cycling performance over CON, but PC showed a possible 2% (30 s, P=0.02) improvement in performance time on climb 2 compared to CON. This improvement was attributed to subjects’ lower perception of effort reported over the first 10 km of the trial, despite no clear performance change during this time. No differences were detected in any other physiological measurements throughout the time trial. Conclusions Despite increasing fluid

  2. Phase II clinical trials with time-to-event endpoints: Optimal two-stage designs with one-sample log-rank test

    PubMed Central

    Kwak, Minjung; Jung, Sin-Ho

    2014-01-01

    Summary Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single-arm phase II clinical trials with right censored survival time responses where the ordinary one-sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials this paper presents two-stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two-stage designs which minimize the maximal sample size are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples. PMID:24338995

  3. Practical modifications to the Time-to-Event Continual Reassessment Method for phase I cancer trials with fast patient accrual and late-onset toxicities

    PubMed Central

    Polley, Mei-Yin C.

    2014-01-01

    The goal of phase I cancer trials is to determine the highest dose of a treatment regimen with an acceptable toxicity rate. Traditional designs for phase I trials, such as the Continual Reassessment Method (CRM) and the 3+3 design, require each patient or a cohort of patients to be fully evaluated for the dose-limiting toxicity (DLT) before new patients can be enrolled. As such, the trial duration may be prohibitively long. The Time-to-Event Continual Reassessment Method (TITE-CRM, Cheung and Chappell, 2000) circumvents this limitation by allowing staggered patient accrual without the need for complete DLT follow-up of previously treated patients. However, in the setting of fast patient accrual and late-onset toxicities, the TITE-CRM results in overly aggressive dose escalation and exposes a considerable number of patients to toxic doses. We examine a modification to the TITE-CRM proposed by the original TITE-CRM creator and propose an alternative approach useful in this setting by incorporating an accrual suspension rule. A simulation study designed based on a neuro-oncology trial indicates that the modified methods provide a much improved degree of safety than the TITE-CRM while maintaining desirable design accuracy. The practical aspects of the proposed designs are discussed. The modifications presented are useful when planning phase I trials involving chemoradiation therapy. PMID:21590790

  4. Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback

    PubMed Central

    Jones, Hollie S.; Williams, Emily L.; Marchant, David; Sparks, S. Andy; Bridge, Craig A.; Midgley, Adrian W.; Mc Naughton, Lars R.

    2016-01-01

    The provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception. Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; (1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, (3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and (4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable. The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes' performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the

  5. Relationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Harrell, Frank E.; Singer, Daniel E.; Becker, Richard C.; Breithardt, Günter; Halperin, Jonathan L.; Hankey, Graeme J.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Background Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons. Methods and Results TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger‐stick point‐of‐care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non‐central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower‐risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non‐major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values. Conclusions The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR. PMID:24755148

  6. A Randomized Trial Comparing Part-time Patching with Observation for Children 3–10 Years Old with Intermittent Exotropia

    PubMed Central

    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.

    2014-01-01

    Objective To determine the effectiveness of prescribed part-time patching for treatment of intermittent exotropia in children Design Multicenter, randomized clinical trial Participants Three hundred fifty-eight children aged 3 to < 11 years old with previously untreated (except for refractive correction) intermittent exotropia (IXT) and near stereoacuity of 400 arcsec or better were enrolled. Intermittent exotropia met the following criteria: 1) constant or intermittent exotropia at distance and either intermittent exotropia or exophoria at near; 2) exodeviation (tropia or phoria) of at least 15 prism diopters (Δ) at distance or near by prism and alternate cover test (PACT); and 3) exodeviation of at least 10Δ at distance by PACT. Methods Participants were randomly assigned to either observation (no treatment for 6 months) or patching for 3 hours per day for 5 months, with a 1-month washout period of no patching before the 6-month primary outcome exam. Main Outcome Measure The primary outcome was deterioration at either the 3-month or the 6-month follow-up visit, defined as: 1) constant exotropia measuring at least 10Δ at distance and near by simultaneous prism and cover test, and/or 2) near stereoacuity decreased by at least 2 octaves from baseline, both assessed by a masked examiner and confirmed by a retest. Participants who were prescribed any non-randomized treatment without first meeting either deterioration criteria were also counted as having deteriorated. Results Of the 324 (91%) participants completing the 6-month primary outcome exam, deterioration occurred in 10 (6.1%) of the 165 participants in the observation group (3 of these 10 started treatment without meeting deterioration criteria) and in 1 (0.6%) of the 159 participants in the part-time patching group (difference = 5.4%, lower limit of one-sided exact 95% confidence interval = 2.0%; p value from one-sided hypothesis test = 0.004). Conclusion Deterioration of previously untreated childhood IXT

  7. A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months Old

    PubMed Central

    Mohney, Brian G.; Cotter, Susan A.; Chandler, Danielle L.; Holmes, Jonathan M.; Chen, Angela M.; Melia, Michele; Donahue, Sean P.; Wallace, David K.; Kraker, Raymond T.; Christian, Melanie L.; Suh, Donny W.

    2015-01-01

    Objective To determine the effectiveness of part-time patching for treating intermittent exotropia (IXT) in young children Design Multicenter, randomized clinical trial Participants Two hundred one children 12 to 35-months-old with untreated IXT meeting the following criteria: 1) IXT at distance OR constant exotropia at distance and either IXT or exophoria at near; 2) ≥15 prism diopter (Δ) exodeviation at distance or near by prism and alternate cover test (PACT) but at least 10Δ exodeviation at distance by PACT. Methods Participants were randomly assigned to either observation (no treatment for 6 months) or patching prescribed for 3 hours daily for 5 months, followed by 1 month of no patching. Main Outcome Measure The primary outcome was deterioration, defined as constant exotropia measuring at least 10Δ at distance and near or receipt of non-protocol treatment for IXT. Results Of the 177 participants (88%) completing the 6-month primary outcome examination, deterioration occurred in 4.6% (4 of 87) of the participants in the observation group and in 2.2% (2 of 90) of the participants in the patching group (difference = 2.4%; P = 0.27, 95% confidence interval (CI) = -3.8% to +9.4%). Motor deterioration occurred in 2.3% (2 of 87) of the observation group and in 2.2% (2 of 90) of the patching group (difference = 0.08%, P = 0.55, 95% CI = -5.8% to +6.1%). For the observation and patching groups respectively, 6-month mean PACT measurements were 27.9Δ versus 24.9Δ at distance (P = 0.02) and 19.3Δ versus 17.0Δ at near (P = 0.10); 6-month mean exotropia control scores were 2.8 vs. 2.3 points at distance (P = 0.02), and 1.4 vs. 1.1 points at near (P = 0.26). Conclusion Among children 12 to 35 months of age with previously untreated IXT, deterioration over 6 months was uncommon, with or without patching treatment. There was insufficient evidence to recommend part-time patching for the treatment of IXT in children in this age group. PMID:26072346

  8. Carbohydrate supplementation improves time-trial cycle performance during energy deficit at 4,300-m altitude.

    PubMed

    Fulco, C S; Kambis, K W; Friedlander, A L; Rock, P B; Muza, S R; Cymerman, A

    2005-09-01

    Carbohydrate supplementation (CHOS) typically improves prolonged time-trial (TT) performance at sea level (SL). This study determined whether CHOS also improves TT performance at high altitude (ALT; 4,300 M) despite increased hypoxemia and while in negative energy balance (approximately 1,250 kcal/day). Two groups of fasting, fitness-matched men performed a 720-kJ cycle TT at SL and while living at ALT on days 3 (ALT3) and 10 (ALT10). Eight men drank a 10% carbohydrate solution (0.175 g/kg body wt) and eight drank a placebo (PLA; double blind) at the start of and every 15 min of the TT. Blood glucose during each TT was higher (P < 0.05) for CHOS than for PLA. At SL, TT duration (approximately 59 min) and watts (approximately 218 or approximately 61% of peak watts; %SL Wpeak) were similar for both groups. At ALT, the TT was longer for both groups (P < 0.01) but was shorter for CHOS than for PLA on ALT3 (means +/- SE: 80 +/- 7 vs. 105 +/- 9 min; P < 0.01) and ALT10 (77 +/- 7 vs. 90 +/- 5 min; P < 0.01). At ALT, %SL Wpeak was reduced (P < 0.01) with the reduction on ALT3 being larger for PLA (to 33 +/- 3%) than for CHOS (to 43 +/- 2%; P < 0.05). On ALT3, O2 saturation fell similarly from 84 +/- 2% at rest to 73 +/- 1% during the TT for both groups (P < 0.05), and on ALT10 O2 saturation fell more (P < 0.02) for CHOS (91 +/- 1 to 76 +/- 2%) than for PLA (90 +/- 1 to 81 +/- 1%). %SL Wpeak and O2 saturation were inversely related during the TT for both groups at ALT (r > or = -0.76; P < or = 0.03). It was concluded that, despite hypoxemia exacerbated by exercise, CHOS greatly improved TT performance at ALT in which there was a negative energy balance.

  9. Cycling time trial performance may be impaired by whey protein and L-alanine intake during prolonged exercise.

    PubMed

    Schroer, Adam B; Saunders, Michael J; Baur, Daniel A; Womack, Christopher J; Luden, Nicholas D

    2014-10-01

    Previous studies reported that adding protein (PRO) to carbohydrate (CHO) solutions enhances endurance performance. The ergogenic effect may be a function of additional protein/amino acid calories, but this has not been examined. In addition, although supplemental L-alanine (ALA) is readily oxidized during exercise, the subsequent impact on metabolism and prolonged endurance performance is unknown. The purpose of this investigation was to independently gauge the impact of whey PRO hydrolysate and ALA supplementation on performance and various physiological parameters. Eight cyclists (age: 22.3 ± 5.6 yr, weight: 70.0 ± 8.0 kg, VO2max: 59.4 ± 4.9 ml · kg(-1) · min(-1)) performed 120 min of constant-load cycling (55% of peak power) followed by a 30-km time trial (TT) under placebo (PLA), PRO, and ALA conditions. Magnitude-based qualitative inferences were applied to evaluate treatment differences and data are presented as percent difference between treatments ± 90% confidence limit. Both ALA (2.1 ± 2.7%) and PRO intake (-2.1 ± 2.2%) possibly harmed performance compared with PLA. Of interest, heart rate was possibly lower with ALA than PLA at 20- (-2.7 ± 3.4%) and 120-min (-1.7 ± 2.9%) of constant-load cycling and the serum interleukin-6 (IL-6) response to 120 min of cycling was likely attenuated with PRO compared with PLA (PLA, 6.6 ± 3.7 fold vs. PRO, 2.9 ± 1.8 fold). In addition, blood glucose levels were lower with PRO than PLA at 20- (-8.8 ± 2.3%; very likely) and 120-min (-4.9 ± 4.6%; likely) of constant-load cycling. Although ALA intake appears to lower HR and PRO ingestion dampens the IL-6 response to exercise, the ingestion of PRO (without CHO) or ALA does not enhance, and may actually impair, performance following prolonged cycling.

  10. Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

    PubMed Central

    2012-01-01

    Background Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Methods/Design Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Discussion Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy

  11. Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

    PubMed

    Hein, Alexander; Gass, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; Lux, Michael P; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Janni, Wolfgang; Fehm, Tanja N; Wallwiener, Diethelm; Ganslandt, Thomas; Ruebner, Matthias; Beckmann, Matthias W; Schneeweiss, Andreas; Fasching, Peter A; Brucker, Sara Y

    2016-07-01

    As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

  12. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  13. Joint modeling of longitudinal ordinal data and competing risks survival times and analysis of the NINDS rt-PA stroke trial

    PubMed Central

    Li, Ning; Elashoff, Robert M.; Li, Gang; Saver, Jeffrey

    2009-01-01

    SUMMARY Existing joint models for longitudinal and survival data are not applicable for longitudinal ordinal outcomes with possible non-ignorable missing values caused by multiple reasons. We propose a joint model for longitudinal ordinal measurements and competing risks failure time data, in which a partial proportional odds model for the longitudinal ordinal outcome is linked to the event times by latent random variables. At the survival endpoint, our model adopts the competing risks framework to model multiple failure types at the same time. The partial proportional odds model, as an extension of the popular proportional odds model for ordinal outcomes, is more flexible and at the same time provides a tool to test the proportional odds assumption. We use a likelihood approach and derive an EM algorithm to obtain the maximum likelihood estimates of the parameters. We further show that all the parameters at the survival endpoint are identifiable from the data. Our joint model enables one to make inference for both the longitudinal ordinal outcome and the failure times simultaneously. In addition, the inference at the longitudinal endpoint is adjusted for possible non-ignorable missing data caused by the failure times. We apply the method to the NINDS rt-PA stroke trial. Our study considers the modified Rankin Scale only. Other ordinal outcomes in the trial, such as the Barthel and Glasgow scales can be treated in the same way. PMID:19943331

  14. A Phase II Randomized Controlled Trial Comparing Safety, Procedure Time, and Cost of the PrePex™ Device to Forceps Guided Surgical Circumcision in Zimbabwe

    PubMed Central

    Tshimanga, Mufuta; Mangwiro, Tonderayi; Mugurungi, Owen; Xaba, Sinokuthemba; Murwira, Munyaradzi; Kasprzyk, Danuta; Montaño, Daniel E.; Nyamukapa, Daisy; Tambashe, Basile; Chatikobo, Pesanai; Gundidza, Patricia; Gwinji, Gerald

    2016-01-01

    Background The World Health Organization (WHO) and the Joint United Nations Program on HIV/AIDS promote MC (male circumcision) as a key HIV prevention strategy where HIV prevalence and incidence are high and MC prevalence is low. In Zimbabwe, to achieve the 1.26 million circumcisions needed to be performed by 2015 to achieve optimal MC coverage, a new approach was needed. The primary objective of the current trial was to assess the performance (safety, procedure time, and cost) of the PrePex device compared to forceps-guided surgical circumcision. Methods and Findings This Phase II, randomized, open-label trial in Zimbabwe involved healthy, non-circumcised adult male volunteers who were randomly assigned to the PrePex device (n = 160) or surgical arm (n = 80). Three doctors and 4 nurses, all certified on both circumcision methods, performed the procedures. The PrePex device procedure involves a plastic ring with a rubber O-ring that necrotizes the foreskin to facilitate easy and minimally invasive removal. Total procedure time was the primary endpoint. Adverse event (AE) data were also gathered for 90 days post-procedure. All 80 participants in the surgical arm and 158 participants in the PrePex arm achieved complete circumcision. The total procedure time for the PrePex device was approximately one-third of the total surgical procedure (4.8 minutes, Standard Deviation [SD]: 1.2 versus 14.6 minutes; SD: 4.2; p<0.00001). There were 2 AEs for 2 participants (rate of 1.3%, 95% Confidence Interval: 0.0025–4.53%), which were resolved with simple intervention. The AEs were device related, including 1 case of pain leading to device removal and 1 case of removal of the device. Conclusions The trial supports previous studies’ conclusions that the PrePex procedure is safe, quick, easy to apply, and effective in terms of procedure time as an alternative to traditional surgical circumcision. The PrePex device has great potential for use in overburdened health systems and in

  15. Reducing bed rest time from five to three hours does not increase complications after cardiac catheterization: the THREE CATH Trial 1

    PubMed Central

    Matte, Roselene; Hilário, Thamires de Souza; Reich, Rejane; Aliti, Graziella Badin; Rabelo-Silva, Eneida Rejane

    2016-01-01

    Abstract Objective: to compare the incidence of vascular complications in patients undergoing transfemoral cardiac catheterization with a 6F introducer sheath followed by 3-hour versus 5-hour rest. Methods: randomized clinical trial. Subjects in the intervention group (IG) ambulated 3 hours after sheath removal, versus 5 hours in the control group (CG). All patients remained in the catheterization laboratory for 5 hours and were assessed hourly, and were contacted 24, 48, and 72 h after hospital discharge. Results: the sample comprised 367 patients in the IG and 363 in the GC. During cath lab stay, hematoma was the most common complication in both groups, occurring in 12 (3%) IG and 13 (4%) CG subjects (P=0.87). Bleeding occurred in 4 (1%) IG and 6 (2%) CG subjects (P=0.51), and vasovagal reaction in 5 (1.4%) IG and 4 (1.1%) CG subjects (P=0.75). At 24-h, 48-h, and 72-h bruising was the most commonly reported complication in both groups. None of the comparisons revealed any significant between-group differences. Conclusion: the results of this trial show that reducing bed rest time to 3 hours after elective cardiac catheterization is safe and does not increase complications as compared with a 5-hour rest. ClinicalTrials.gov Identifier: NCT-01740856 PMID:27463113

  16. 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.

    PubMed

    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

  17. Timing of eyewitness expert testimony, jurors' need for cognition, and case strength as determinants of trial verdicts.

    PubMed

    Leippe, Michael R; Eisenstadt, Donna; Rauch, Shannon M; Seib, Hope M

    2004-06-01

    In 2 experiments, college students read a murder-trial transcript that included or did not include court-appointed expert testimony about eyewitness memory. The testimony either preceded or followed the evidence, and the judge's final instructions reminded or did not remind jurors about the expert's testimony. Expert testimony decreased perceptions of guilt and eyewitness believability when it followed the evidence and preceded the judge's reminder. This effect occurred whether the prosecution case was moderately weak or moderately strong. Jurors' need for cognition (NC) was curvilinearly related to convictions in a strong case. Low and high NC jurors convicted less than did moderate NC jurors. Greater scrutiny by high NC jurors may make them more likely to consider evidence for the weaker side. PMID:15161410

  18. Time-dependent effects of aspirin on blood pressure and morning platelet reactivity: a randomized cross-over trial.

    PubMed

    Bonten, Tobias N; Snoep, Jaapjan D; Assendelft, Willem J J; Zwaginga, Jaap Jan; Eikenboom, Jeroen; Huisman, Menno V; Rosendaal, Frits R; van der Bom, Johanna G

    2015-04-01

    Aspirin is used for cardiovascular disease (CVD) prevention by millions of patients on a daily basis. Previous studies suggested that aspirin intake at bedtime reduces blood pressure compared with intake on awakening. This has never been studied in patients with CVD. Moreover, platelet reactivity and CVD incidence is highest during morning hours. Bedtime aspirin intake may attenuate morning platelet reactivity. This clinical trial examined the effect of bedtime aspirin intake compared with intake on awakening on 24-hour ambulatory blood pressure measurement and morning platelet reactivity in patients using aspirin for CVD prevention. In this randomized open-label crossover trial, 290 patients were randomized to take 100 mg aspirin on awakening or at bedtime during 2 periods of 3 months. At the end of each period, 24-hour blood pressure and morning platelet reactivity were measured. The primary analysis population comprised 263 (blood pressure) and 133 (platelet reactivity) patients. Aspirin intake at bedtime did not reduce blood pressure compared with intake on awakening (difference systolic/diastolic: -0.1 [95% confidence interval, -1.0, 0.9]/-0.6 [95% confidence interval, -1.2, 0.0] mm Hg). Platelet reactivity during morning hours was reduced with bedtime aspirin intake (difference: -22 aspirin reaction units [95% confidence interval, -35, -9]). The intake of low-dose aspirin at bedtime compared with intake on awakening did not reduce blood pressure of patients with CVD. However, bedtime aspirin reduced morning platelet reactivity. Future studies are needed to assess the effect of this promising simple intervention on the excess of cardiovascular events during the high risk morning hours.

  19. DiAs Web Monitoring: A Real-Time Remote Monitoring System Designed for Artificial Pancreas Outpatient Trials

    PubMed Central

    Place, Jérôme; Robert, Antoine; Brahim, Najib Ben; Patrick, Keith-Hynes; Farret, Anne; Marie-Josée, Pelletier; Buckingham, Bruce; Breton, Marc; Kovatchev, Boris; Renard, Eric

    2013-01-01

    Background Developments in an artificial pancreas (AP) for patients with type 1 diabetes have allowed a move toward performing outpatient clinical trials. “Home-like” environment implies specific protocol and system adaptations among which the introduction of remote monitoring is meaningful. We present a novel tool allowing multiple patients to monitor AP use in home-like settings. Methods We investigated existing systems, performed interviews of experienced clinical teams, listed required features, and drew several mockups of the user interface. The resulting application was tested on the bench before it was used in three outpatient studies representing 3480 h of remote monitoring. Results Our tool, called DiAs Web Monitoring (DWM), is a web-based application that ensures reception, storage, and display of data sent by AP systems. Continuous glucose monitoring (CGM) and insulin delivery data are presented in a colored chart to facilitate reading and interpretation. Several subjects can be monitored simultaneously on the same screen, and alerts are triggered to help detect events such as hypoglycemia or CGM failures. In the third trial, DWM received approximately 460 data per subject per hour: 77% for log messages, 5% for CGM data. More than 97% of transmissions were achieved in less than 5 min. Conclusions Transition from a hospital setting to home-like conditions requires specific AP supervision to which remote monitoring systems can contribute valuably. DiAs Web Monitoring worked properly when tested in our outpatient studies. It could facilitate subject monitoring and even accelerate medical and technical assessment of the AP. It should now be adapted for long-term studies with an enhanced notification feature. J Diabetes Sci Technol 2013;7(6):1427–1435 PMID:24351169

  20. Quasi-experimental trial of diabetes Self-Management Automated and Real-Time Telephonic Support (SMARTSteps) in a Medicaid managed care plan: study protocol

    PubMed Central

    2012-01-01

    Background Health information technology can enhance self-management and quality of life for patients with chronic disease and overcome healthcare barriers for patients with limited English proficiency. After a randomized controlled trial of a multilingual automated telephone self-management support program (ATSM) improved patient-centered dimensions of diabetes care in safety net clinics, we collaborated with a nonprofit Medicaid managed care plan to translate research into practice, offering ATSM as a covered benefit and augmenting ATSM to promote medication activation. This paper describes the protocol of the Self-Management Automated and Real-Time Telephonic Support Project (SMARTSteps). Methods/Design This controlled quasi-experimental trial used a wait-list variant of a stepped wedge design to enroll 362 adult health plan members with diabetes who speak English, Cantonese, or Spanish and receive care at 4 publicly-funded clinics. Through language-stratified randomization, participants were assigned to four intervention statuses: SMARTSteps-ONLY, SMARTSteps-PLUS, or wait-list for either intervention. In addition to usual primary care, intervention participants received 27 weekly calls in their preferred language with rotating queries and response-triggered education about self-care, medication adherence, safety concerns, psychological issues, and preventive services. Health coaches from the health plan called patients with out-of-range responses for collaborative goal setting and action planning. SMARTSteps-PLUS also included health coach calls to promote medication activation, adherence and intensification, if triggered by ATSM-reported non-adherence, refill non-adherence from pharmacy claims, or suboptimal cardiometabolic indicators. Wait-list patients crossed-over to SMARTSteps-ONLY or -PLUS at 6 months. For participants who agreed to structured telephone interviews at baseline and 6 months (n = 252), primary outcomes will be changes in quality of life and

  1. Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

    PubMed Central

    Tovanabutra, Sodsai; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Eamsila, Chirapa; Kunasol, Prayura; Khamboonruang, Chirasak; Thongcharoen, Prasert; Namwat, Chawetsan; Premsri, Nakorn; Benenson, Michael; Morgan, Patricia; Bose, Meera; Sanders-Buell, Eric; Paris, Robert; Robb, Merlin L.; Birx, Deborah L.; De Souza, Mark S.; McCutchan, Francine E.; Michael, Nelson L.; Kim, Jerome H.

    2013-01-01

    The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results. PMID:23576510

  2. Different time course for prevention of coronary and stroke events by atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA).

    PubMed

    Sever, Peter S; Poulter, Neil R; Dahlöf, Björn; Wedel, Hans

    2005-09-01

    The lipid-lowering properties of statins reduce rates of coronary artery disease (CAD) events and strokes. Findings of recently conducted, longitudinal intervention studies suggest that these benefits occur early and may be, in part, independent of the lipid-lowering properties of statin therapy. We analyzed data from the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA) to determine the timing of cardiovascular risk reduction. Relative risk reductions in CAD events were large compared with placebo, becoming apparent at 30 days and significant within 3 months, but they tended to decrease with time. Risk reductions in stroke were also apparent at 30 days but remained constant throughout the trial. Significant differences in hazard ratio between atorvastatin and placebo occurred at 2-year follow-up. Such apparently differential effects on CAD and stroke events suggest that mechanisms of action for CAD and stroke prevention may be different. These observations support the hypothesis that non-lipid-lowering actions of atorvastatin may have contributed to early protection against CAD in ASCOT-LLA.

  3. Balloon dilation of benign esophageal rings or strictures: a randomized clinical trial comparing two different inflation times.

    PubMed

    Wallner, O; Wallner, B

    2014-01-01

    Although balloon dilatation is the primary treatment for benign dysphagia, information about the optimal inflation time is lacking. The aim of the current pilot study was to compare 10 seconds inflation time with 2 minutes inflation time, regarding the efficacy. Twenty patients with symptomatic strictures were prospectively studied in a randomized fashion. The 10-second group required an average of 1.4 dilations per patient; the 2-minute group required an average of 1.5 dilations per patient. This pilot study indicates that 10 seconds inflation time is as effective as 2 minutes. Because the treatment is both painful and unpleasant, this is an important finding.

  4. Prior Low- or High-Intensity Exercise Alters Pacing Strategy, Energy System Contribution and Performance during a 4-km Cycling Time Trial

    PubMed Central

    Correia-Oliveira, Carlos Rafaell; Santos, Ralmony Alcantara; Silva-Cavalcante, Marcos David; Bertuzzi, Romulo; Kiss, Maria Augusta Peduti Dal’Molin; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    We analyzed the influence of prior exercise designed to reduce predominantly muscle glycogen in either type I or II fibers on pacing and performance during a 4-km cycling time trial (TT). After preliminary and familiarization trials, in a randomized, repeated-measures crossover design, ten amateur cyclists performed: 1) an exercise designed to reduce glycogen of type I muscle fibers, followed by a 4-km TT (EX-FIB I); 2) an exercise designed to reduce glycogen of type II muscle fibers, followed by a 4-km TT (EX-FIB II) and; 3) a 4-km TT, without the prior exercise (CONT). The muscle-glycogen-reducing exercise in both EX-FIB I and EX-FIB II was performed in the evening, ∼12 h before the 4-km TT. Performance time was increased and power output (PO) was reduced in EX-FIB I (432.8±8.3 s and 204.9±10.9 W) and EX-FIB II (428.7±6.7 s and 207.5±9.1 W) compared to CONT (420.8±6.4 s and 218.4±9.3 W; P<0.01), without a difference between EX-FIB I and EX-FIB II (P>0.05). The PO was lower in EX-FIB I than in CONT at the beginning and middle of the trial (P<0.05). The mean aerobic contribution during EX-FIB I was also significantly lower than in CONT (P<0.05), but there was no difference between CONT and EX-FIB II or between EX-FIB I and EX-FIB II (P>0.05). The integrated electromyography was unchanged between conditions (P>0.05). Performance may have been impaired in EX-FIB I due a more conservative pacing at the beginning and middle, which was associated with a reduced aerobic contribution. In turn, the PO profile adopted in EX-FIB II was also reduced throughout the trial, but the impairment in performance may be attributed to a reduced glycolytic contribution (i.e. reduced lactate accumulation). PMID:25330452

  5. Prior low- or high-intensity exercise alters pacing strategy, energy system contribution and performance during a 4-km cycling time trial.

    PubMed

    Correia-Oliveira, Carlos Rafaell; Santos, Ralmony Alcantara; Silva-Cavalcante, Marcos David; Bertuzzi, Romulo; Kiss, Maria Augusta Peduti Dal'Molin; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    We analyzed the influence of prior exercise designed to reduce predominantly muscle glycogen in either type I or II fibers on pacing and performance during a 4-km cycling time trial (TT). After preliminary and familiarization trials, in a randomized, repeated-measures crossover design, ten amateur cyclists performed: 1) an exercise designed to reduce glycogen of type I muscle fibers, followed by a 4-km TT (EX-FIB I); 2) an exercise designed to reduce glycogen of type II muscle fibers, followed by a 4-km TT (EX-FIB II) and; 3) a 4-km TT, without the prior exercise (CONT). The muscle-glycogen-reducing exercise in both EX-FIB I and EX-FIB II was performed in the evening, ∼12 h before the 4-km TT. Performance time was increased and power output (PO) was reduced in EX-FIB I (432.8±8.3 s and 204.9±10.9 W) and EX-FIB II (428.7±6.7 s and 207.5±9.1 W) compared to CONT (420.8±6.4 s and 218.4±9.3 W; P<0.01), without a difference between EX-FIB I and EX-FIB II (P>0.05). The PO was lower in EX-FIB I than in CONT at the beginning and middle of the trial (P<0.05). The mean aerobic contribution during EX-FIB I was also significantly lower than in CONT (P<0.05), but there was no difference between CONT and EX-FIB II or between EX-FIB I and EX-FIB II (P>0.05). The integrated electromyography was unchanged between conditions (P>0.05). Performance may have been impaired in EX-FIB I due a more conservative pacing at the beginning and middle, which was associated with a reduced aerobic contribution. In turn, the PO profile adopted in EX-FIB II was also reduced throughout the trial, but the impairment in performance may be attributed to a reduced glycolytic contribution (i.e. reduced lactate accumulation).

  6. Optimal blood sampling time windows for parameter estimation using a population approach: design of a phase II clinical trial.

    PubMed

    Chenel, Marylore; Ogungbenro, Kayode; Duval, Vincent; Laveille, Christian; Jochemsen, Roeline; Aarons, Leon

    2005-12-01

    The objective of this paper is to determine optimal blood sampling time windows for the estimation of pharmacokinetic (PK) parameters by a population approach within the clinical constraints. A population PK model was developed to describe a reference phase II PK dataset. Using this model and the parameter estimates, D-optimal sampling times were determined by optimising the determinant of the population Fisher information matrix (PFIM) using PFIM_ _M 1.2 and the modified Fedorov exchange algorithm. Optimal sampling time windows were then determined by allowing the D-optimal windows design to result in a specified level of efficiency when compared to the fixed-times D-optimal design. The best results were obtained when K(a) and IIV on K(a) were fixed. Windows were determined using this approach assuming 90% level of efficiency and uniform sample distribution. Four optimal sampling time windows were determined as follow: at trough between 22 h and new drug administration; between 2 and 4 h after dose for all patients; and for 1/3 of the patients only 2 sampling time windows between 4 and 10 h after dose, equal to [4 h-5 h 05] and [9 h 10-10 h]. This work permitted the determination of an optimal design, with suitable sampling time windows which was then evaluated by simulations. The sampling time windows will be used to define the sampling schedule in a prospective phase II study.

  7. Preliminary Comparison of Two-Way Satellite Time and Frequency Transfer and GPS Common-View Time Transfer During the INTELSAT Field Trial

    NASA Technical Reports Server (NTRS)

    Davis, John A.; Lewandowski, W.; DeYoung, James A.; Kirchner, Dieter; Hetzel, Peter; deJong, Gerrit; Soering, A.; Baumont, F.; Klepczynski, William; McKinley, Angela Davis; Parker, Thomas E.; Bartle, K. A.; Ressler, Hubert; Robnik, R.; Veenstra, L.

    1996-01-01

    For a decade and a half Global Positioning System (GPS) common-view time transfer has greatly served the needs of primary timing laboratories for regular intercomparisons of remote atomic clocks. However, GPS as a one-way technique has natural limits and may not meet all challenges of the comparison of the coming new generation of atomic clocks. Two-way satellite time and frequency transfer (TWSTFT) is a promising technique which may successfully complement GPS. For two years, regular TWSTFT's have been performed between eight laboratories situated in both Europe and North America, using INTELSAT satellites. This has enabled an extensive direct comparison to be made between these two high performance time transfer methods. The performance of the TWSTFT and GPS common view methods are compared over a number of time-transfer links. These links use a variety of time-transfer hardware and atomic clocks and have baselines of substantially different lengths. The relative merits of the two time-transfer systems are discussed.

  8. Clinical trial: assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology

    PubMed Central

    Sarosiek, I.; Selover, K. H.; Katz, L. A.; Semler, J. R.; Wilding, G. E.; Lackner, J. M.; Sitrin, M. D.; Kuo, B.; Chey, W. D.; Hasler, W. L.; Koch, K. L.; Parkman, H. P.; Sarosiek, J; Mccallum, R. W.

    2015-01-01

    BACKGROUND Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. AIMS Data from a multi-center study of gastroparetic patients and healthy controls was analyzed to: compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). METHODS 66 healthy controls and 34 patients with GP [15 diabetic and 19 idiopathic] swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), and whole gut transit time (WGTT) were calculated using the wireless motility capsule. RESULTS GET, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic etiologies of gastroparetics had significantly slower WGTT (p<0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (p = 0.0054). CONCLUSIONS 1) In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. 2) The prolongation of CTT in gastroparetic patients indicates dysmotility beyond the stomach in GP is present and could be contributing to symptom presentation. PMID:19814743

  9. Two-Arm Randomized Pilot Intervention Trial to Decrease Sitting Time and Increase Sit-To-Stand Transitions in Working and Non-Working Older Adults

    PubMed Central

    Kerr, Jacqueline; Takemoto, Michelle; Bolling, Khalisa; Atkin, Andrew; Carlson, Jordan; Rosenberg, Dori; Crist, Katie; Godbole, Suneeta; Lewars, Brittany; Pena, Claudia; Merchant, Gina

    2016-01-01

    Background Excessive sitting has been linked to poor health. It is unknown whether reducing total sitting time or increasing brief sit-to-stand transitions is more beneficial. We conducted a randomized pilot study to assess whether it is feasible for working and non-working older adults to reduce these two different behavioral targets. Methods Thirty adults (15 workers and 15 non-workers) age 50–70 years were randomized to one of two conditions (a 2-hour reduction in daily sitting or accumulating 30 additional brief sit-to-stand transitions per day). Sitting time, standing time, sit-to-stand transitions and stepping were assessed by a thigh worn inclinometer (activPAL). Participants were assessed for 7 days at baseline and followed while the intervention was delivered (2 weeks). Mixed effects regression analyses adjusted for days within participants, device wear time, and employment status. Time by condition interactions were investigated. Results Recruitment, assessments, and intervention delivery were feasible. The ‘reduce sitting’ group reduced their sitting by two hours, the ‘increase sit-to-stand’ group had no change in sitting time (p < .001). The sit-to-stand transition group increased their sit-to-stand transitions, the sitting group did not (p < .001). Conclusions This study was the first to demonstrate the feasibility and preliminary efficacy of specific sedentary behavioral goals. Trial Registration clinicaltrials.gov NCT02544867 PMID:26735919

  10. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials

    PubMed Central

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-01-01

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993. PMID:26950143

  11. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials.

    PubMed

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-03-01

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993. PMID:26950143

  12. Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

    PubMed

    Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

    2009-10-14

    Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods.

  13. The P600-as-P3 hypothesis revisited: single-trial analyses reveal that the late EEG positivity following linguistically deviant material is reaction time aligned.

    PubMed

    Sassenhagen, Jona; Schlesewsky, Matthias; Bornkessel-Schlesewsky, Ina

    2014-10-01

    The P600, a late positive ERP component following linguistically deviant stimuli, is commonly seen as indexing structural, high-level processes, e.g. of linguistic (re)analysis. It has also been identified with the P3 (P600-as-P3 hypothesis), which is thought to reflect a systemic neuromodulator release facilitating behavioural shifts and is usually response time aligned. We investigated single-trial alignment of the P600 to response, a critical prediction of the P600-as-P3 hypothesis. Participants heard sentences containing morphosyntactic and semantic violations and responded via a button press. The elicited P600 was perfectly response aligned, while an N400 following semantic deviations was stimulus aligned. This is, to our knowledge, the first single-trial analysis of language processing data using within-sentence behavioural responses as temporal covariates. Results support the P600-as-P3 perspective and thus constitute a step towards a neurophysiological grounding of language-related ERPs.

  14. Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

    PubMed

    Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

    2009-10-14

    Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods. PMID:19807158

  15. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  16. The effectiveness of critical time intervention for abused women and homeless people leaving Dutch shelters: study protocol of two randomised controlled trials

    PubMed Central

    2013-01-01

    Background One of the main priorities of Dutch organisations providing shelter services is to develop evidence-based interventions in the care for abused women and homeless people. To date, most of these organisations have not used specific intervention models and the interventions which have been implemented rarely have an empirical and theoretical foundation. The present studies aim to examine the effectiveness of critical time intervention (CTI) for abused women and homeless people. Methods In two multi-centre randomised controlled trials we investigate whether CTI, a time-limited (nine month) outreach intervention, is more effective than care-as-usual for abused women and homeless people making the transition from shelter facilities to supported or independent housing. Participants were recruited in 19 women’s shelter facilities and 22 homeless shelter facilities across The Netherlands and randomly allocated to the intervention group (CTI) or the control group (care-as-usual). They were interviewed four times in nine months: once before leaving the shelter, and then at three, six and nine months after leaving the shelter. Quality of life (primary outcome for abused women) and recurrent loss of housing (primary outcome for homeless people) as well as secondary outcomes (e.g. care needs, self-esteem, loneliness, social support, substance use, psychological distress and service use) were assessed during the interviews. In addition, the model integrity of CTI was investigated during the data collection period. Discussion Based on international research CTI is expected to be an appropriate intervention for clients making the transition from institutional to community living. If CTI proves to be effective for abused women and homeless people, shelter services could include this case management model in their professional standards and improve the (quality of) services for clients. Trial registration NTR3463 and NTR3425 PMID:25927562

  17. Making Time for Instructional Leadership. Volume 2: The Feasibility of a Randomized Control Trial of the SAM Process

    ERIC Educational Resources Information Center

    Goldring, Ellen; Grissom, Jason A.; Neumerski, Christine M.; Murphy, Joseph; Blissett, Richard; Porter, Andy

    2015-01-01

    This three-volume report describes the "SAM (School Administration Manager) process," an approach that about 700 schools around the nation are using to direct more of principals' time and effort to improve teaching and learning in classrooms. Research has shown that a principal's instructional leadership is second only to teaching among…

  18. Trial Watch

    PubMed Central

    Vacchelli, Erika; Aranda, Fernando; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects. These three classes of mAbs exert antineoplastic activity via distinct mechanisms, which may or may not involve immune effectors other than the mAbs themselves. In previous issues of OncoImmunology, we provided a brief scientific background to the use of mAbs, all types confounded, in cancer therapy, and discussed the results of recent clinical trials investigating the safety and efficacy of this approach. Here, we focus on mAbs that primarily target malignant cells or their interactions with stromal components, as opposed to mAbs that mediate antineoplastic effects by activating the immune system. In particular, we discuss relevant clinical findings that have been published during the last 13 months as well as clinical trials that have been launched in the same period to investigate the therapeutic profile of hitherto investigational tumor-targeting mAbs. PMID:24605265

  19. Indicators of early and late processing reveal the importance of within-trial-time for theories of associative learning.

    PubMed

    Lachnit, Harald; Thorwart, Anna; Schultheis, Holger; Lotz, Anja; Koenig, Stephan; Uengoer, Metin

    2013-01-01

    In four human learning experiments (Pavlovian skin conductance, causal learning, speeded classification task), we evaluated several associative learning theories that assume either an elemental (modified unique cue model and Harris' model) or a configural (Pearce's configural theory and an extension of it) form of stimulus processing. The experiments used two modified patterning problems (A/B/C+, AB/BC/AC+ vs. ABC-; A+, BC+ vs. ABC-). Pearce's configural theory successfully predicted all of our data reflecting early stimulus processing, while the predictions of the elemental theories were in accord with all of our data reflecting later stages of stimulus processing. Our results suggest that the form of stimulus representation depends on the amount of time available for stimulus processing. Our findings highlight the necessity to investigate stimulus processing during conditioning on a finer time scale than usually done in contemporary research.

  20. Indicators of Early and Late Processing Reveal the Importance of Within-Trial-Time for Theories of Associative Learning

    PubMed Central

    Lachnit, Harald; Thorwart, Anna; Schultheis, Holger; Lotz, Anja; Koenig, Stephan; Uengoer, Metin

    2013-01-01

    In four human learning experiments (Pavlovian skin conductance, causal learning, speeded classification task), we evaluated several associative learning theories that assume either an elemental (modified unique cue model and Harris’ model) or a configural (Pearce’s configural theory and an extension of it) form of stimulus processing. The experiments used two modified patterning problems (A/B/C+, AB/BC/AC+ vs. ABC-; A+, BC+ vs. ABC-). Pearce’s configural theory successfully predicted all of our data reflecting early stimulus processing, while the predictions of the elemental theories were in accord with all of our data reflecting later stages of stimulus processing. Our results suggest that the form of stimulus representation depends on the amount of time available for stimulus processing. Our findings highlight the necessity to investigate stimulus processing during conditioning on a finer time scale than usually done in contemporary research. PMID:23826092

  1. Real-time differential GPS/GLONASS trials in Europe using all-in-view 20-channel receivers

    NASA Astrophysics Data System (ADS)

    Capaccio, S.; Lowe, D.; Walsh, D. M. A.; Daly, P.

    Following the initial development of 20-channel, all-in-view Global Navigation Satellite System (GNSS), GPS/GLONASS/Inmarsat-3, receivers at the Institute of Satellite Navigation (ISN), University of Leeds, a modification programme has been undertaken to allow real-time differential corrections to be sent from one 20-channel receiver to another identical receiver using a serial link between them. The differential correction software incorporates the RTCM SC-104 and RTCA DO-217 format developed specifically for GPS and adjusted by the ISN to allow simultaneous GLONASS operation.After successful laboratory testing, real-time differential GNSS tests were successfully completed in static mode between Aberdeen and Leeds via the SkyFix differential data-link, and in dynamic mode at DTEO Boscombe Down using a C-band data-link between the ground and a receiver on board the DRA BAC 1-11 aircraft. The aims of the tests were, (i) to demonstrate real-time differential GNSS position-fixing, (ii) to establish the accuracy improvements brought about, and (iii) to examine the effects of data-link latency and satellite PDOP on the solution accuracy.

  2. International ring trial for the validation of an event-specific Golden Rice 2 quantitative real-time polymerase chain reaction method.

    PubMed

    Jacchia, Sara; Nardini, Elena; Bassani, Niccolò; Savini, Christian; Shim, Jung-Hyun; Trijatmiko, Kurniawan; Kreysa, Joachim; Mazzara, Marco

    2015-05-27

    This article describes the international validation of the quantitative real-time polymerase chain reaction (PCR) detection method for Golden Rice 2. The method consists of a taxon-specific assay amplifying a fragment of rice Phospholipase D α2 gene, and an event-specific assay designed on the 3' junction between transgenic insert and plant DNA. We validated the two assays independently, with absolute quantification, and in combination, with relative quantification, on DNA samples prepared in haploid genome equivalents. We assessed trueness, precision, efficiency, and linearity of the two assays, and the results demonstrate that both the assays independently assessed and the entire method fulfill European and international requirements for methods for genetically modified organism (GMO) testing, within the dynamic range tested. The homogeneity of the results of the collaborative trial between Europe and Asia is a good indicator of the robustness of the method. PMID:25946377

  3. International ring trial for the validation of an event-specific Golden Rice 2 quantitative real-time polymerase chain reaction method.

    PubMed

    Jacchia, Sara; Nardini, Elena; Bassani, Niccolò; Savini, Christian; Shim, Jung-Hyun; Trijatmiko, Kurniawan; Kreysa, Joachim; Mazzara, Marco

    2015-05-27

    This article describes the international validation of the quantitative real-time polymerase chain reaction (PCR) detection method for Golden Rice 2. The method consists of a taxon-specific assay amplifying a fragment of rice Phospholipase D α2 gene, and an event-specific assay designed on the 3' junction between transgenic insert and plant DNA. We validated the two assays independently, with absolute quantification, and in combination, with relative quantification, on DNA samples prepared in haploid genome equivalents. We assessed trueness, precision, efficiency, and linearity of the two assays, and the results demonstrate that both the assays independently assessed and the entire method fulfill European and international requirements for methods for genetically modified organism (GMO) testing, within the dynamic range tested. The homogeneity of the results of the collaborative trial between Europe and Asia is a good indicator of the robustness of the method.

  4. Organizational-Level Strategies With or Without an Activity Tracker to Reduce Office Workers’ Sitting Time: Rationale and Study Design of a Pilot Cluster-Randomized Trial

    PubMed Central

    Fjeldsoe, Brianna S; Young, Duncan C; Winkler, Elisabeth A H; Dunstan, David W; Straker, Leon M; Brakenridge, Christian J; Healy, Genevieve N

    2016-01-01

    Background The office workplace is a key setting in which to address excessive sitting time and inadequate physical activity. One major influence on workplace sitting is the organizational environment. However, the impact of organizational-level strategies on individual level activity change is unknown. Further, the emergence of sophisticated, consumer-targeted wearable activity trackers that facilitate real-time self-monitoring of activity, may be a useful adjunct to support organizational-level strategies, but to date have received little evaluation in this workplace setting. Objective The aim of this study is to evaluate the feasibility, acceptability, and effectiveness of organizational-level strategies with or without an activity tracker on sitting, standing, and stepping in office workers in the short (3 months, primary aim) and long-term (12 months, secondary aim). Methods This study is a pilot, cluster-randomized trial (with work teams as the unit of clustering) of two interventions in office workers: organizational-level support strategies (eg, visible management support, emails) or organizational-level strategies plus the use of a waist-worn activity tracker (the LUMOback) that enables self-monitoring of sitting, standing, and stepping time and enables users to set sitting and posture alerts. The key intervention message is to ‘Stand Up, Sit Less, and Move More.’ Intervention elements will be implemented from within the organization by the Head of Workplace Wellbeing. Participants will be recruited via email and enrolled face-to-face. Assessments will occur at baseline, 3, and 12 months. Time spent sitting, sitting in prolonged (≥30 minute) bouts, standing, and stepping during work hours and across the day will be measured with activPAL3 activity monitors (7 days, 24 hours/day protocol), with total sitting time and sitting time during work hours the primary outcomes. Web-based questionnaires, LUMOback recorded data, telephone interviews, and focus

  5. Effects of Six versus Three Times per Week Hemodialysis on Physical Performance, Health, and Functioning: Frequent Hemodialysis Network (FHN) Randomized Trials

    PubMed Central

    Larive, Brett; Painter, Patricia; Kaysen, George A.; Lindsay, Robert M.; Nissenson, Allen R.; Unruh, Mark L.; Rocco, Michael V.; Chertow, Glenn M.

    2012-01-01

    Summary Background and objectives Relatively little is known about the effects of hemodialysis frequency on the disability of patients with ESRD. Design, setting, participants, & measurements This study examined changes in physical performance and self-reported physical health and functioning among subjects randomized to frequent (six times per week) compared with conventional (three times per week) hemodialysis in both the Frequent Hemodialysis Network daily (n=245) and nocturnal (n=87) trials. The main outcome measures were adjusted change in scores over 12 months on the short physical performance battery (SPPB), RAND 36-item health survey physical health composite (PHC), and physical functioning subscale (PF) based on the intention to treat principle. Results Overall scores for SPPB, PHC, and PF were poor relative to population norms and in line with other studies in ESRD. In the Daily Trial, subjects randomized to frequent compared with conventional in-center hemodialysis experienced no significant change in SPPB (adjusted mean change of −0.20±0.19 versus −0.41±0.21, P=0.45) but experienced significant improvement in PHC (3.4±0.8 versus 0.4±0.8, P=0.009) and a relatively large change in PF that did not reach statistical significance. In the Nocturnal Trial, there were no significant differences among subjects randomized to frequent compared with conventional hemodialysis in SPPB (adjusted mean change of −0.92±0.44 versus −0.41±0.43, P=0.41), PHC (2.7±1.4 versus 2.1±1.5, P=0.75), or PF (−3.1±3.5 versus 1.1±3.6, P=0.40). Conclusions Frequent in-center hemodialysis compared with conventional in-center hemodialysis improved self-reported physical health and functioning but had no significant effect on objective physical performance. There were no significant effects of frequent nocturnal hemodialysis on the same physical metrics. PMID:22422538

  6. Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial

    PubMed Central

    Hambardzumyan, Karen; Bolce, Rebecca J; Saevarsdottir, Saedis; Forslind, Kristina; Wallman, Johan K; Cruickshank, Scott E; Sasso, Eric H; Chernoff, David; van Vollenhoven, Ronald F

    2016-01-01

    Objectives In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up. Methods A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2. Results Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30–44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy. Conclusions Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP. Trial registration number NCT00764725. PMID:26958364

  7. A moderate dose of caffeine ingestion does not change energy expenditure but decreases sleep time in physically active males: a double-blind randomized controlled trial.

    PubMed

    Júdice, Pedro B; Magalhães, João P; Santos, Diana A; Matias, Catarina N; Carita, Ana Isabel; Armada-Da-Silva, Paulo A S; Sardinha, Luís B; Silva, Analiza M

    2013-01-01

    Research on the effect of caffeine on energy expenditure (EE), physical activity (PA), and total sleep time (TST) during free-living conditions using objective measures is scarce. We aimed to determine the impact of a moderate dose of caffeine on TST, resting EE (REE), physical activity EE (PAEE), total EE (TEE), and daily time spent in sedentary, light, moderate, and vigorous intensity activities in a 4-day period and the acute effects on heart rate (HR) and EE in physically active males. Using a double-blind crossover trial (ClinicalTrials.gov ID: NCT01477294) with two conditions (4 days each with 3-day washout) randomly ordered as caffeine (5 mg/kg of body mass/day) and placebo (maltodextrin) administered twice per day (2.5 mg/kg), 30 nonsmoker males, low-caffeine users (<100 mg/day), aged 20-39, were followed. Body composition was assessed by dual-energy X-ray absorptiometry. PA was assessed by accelerometry, while a combined HR and movement sensor estimated EE and HR on the second hour after the first administration dose. REE was assessed by indirect calorimetry, and PAEE was calculated as [TEE - (REE + 0.1TEE)]. TST and daily food records were obtained. Repeated measures ANOVA and ANCOVA were used. After a 4-day period, adjusting for fat-free mass, PAEE, and REE, TST was reduced (p = 0.022) under caffeine intake, while no differences were found between conditions for REE, PAEE, TEE, and PA patterns. Also, no acute effects on HR and EE were found between conditions. Though a large individual variability was observed, our findings revealed no acute or long-term effects of caffeine on EE and PA but decreased TST during free-living conditions in healthy males.

  8. To determine block establishment time of supraclavicular brachial plexus block using blunt versus short bevel needle: A prospective randomized trial

    PubMed Central

    Ahuja, V; Thapa, D; Gombar, S; Dhiman, D

    2016-01-01

    Background: Unintentional intraneural injection under ultrasound guidance (USG) with fine caliber needles and lower success rate with large caliber Tuohy needles in supraclavicular brachial plexus block (SCB) have been reported. Materials and Methods: We undertook study to standardize the use of 20-gauge short versus blunt bevel needle for SCB. After approval of Institutional Ethics Committee and written informed consent, patients were randomized using computer-generated random number table to either of the two groups; blunt bevel needle group (n = 30): SCB under USG using 20-gauge Tuohy needle or short bevel needle group (n = 30): SCB under USG using 20-gauge short bevel needle. The primary outcome of the study was time to establishment of sensory and motor block of individual nerves, and secondary outcome was tolerability and any adverse effects. Results: The time to establishment of sensory and motor block in individual nerve territory was similar in both the groups. The complete sensory and motor anesthesia was achieved in 78.3% patients and complete sensory and motor anesthesia after supplementary block was achieved in 86.6% patients. Paresthesias during SCB were recorded in 15 patients. Out of these eight patients were of blunt bevel group and seven patients were of short bevel group. None of the patients experienced any neurological adverse effects. Conclusion: The establishment of sensory and motor blockade of individual nerves was similar to 20-gauge short and blunt bevel needle under ultrasound guide with no neurological adverse events. PMID:27375378

  9. The better the story, the bigger the serving: narrative transportation increases snacking during screen time in a randomized trial

    PubMed Central

    2013-01-01

    Background Watching television and playing video games increase energy intake, likely due to distraction from satiety cues. A study comparing one hour of watching TV, playing typical video games, or playing motion-controlled video games found a difference across groups in energy intake, but the reasons for this difference are not clear. As a secondary analysis, we investigated several types of distraction to determine potential psychosocial mechanisms which may account for greater energy intake observed during sedentary screen time as compared to motion-controlled video gaming. Methods Feelings of enjoyment, engagement (mental immersion), spatial presence (the feeling of being in the game), and transportation (immersion in a narrative) were investigated in 120 young adults aged 18 – 35 (60 female). Results Only narrative transportation was associated with total caloric intake (ρ = .205, P = .025). Transportation was also higher in the TV group than in the gaming groups (P = .002) and higher in males than in females (P = .003). Transportation mediated the relationship between motion-controlled gaming (as compared to TV watching) and square root transformed energy intake (indirect effect = −1.34, 95% confidence interval −3.57, −0.13). No other distraction-related variables were associated with intake. Conclusions These results suggest that different forms of distraction may differentially affect eating behavior during screen time, and that narrative appears to be a particularly strong distractor. Future studies should further investigate the effects of narrative on eating behavior. PMID:23680389

  10. V-TIME: a treadmill training program augmented by virtual reality to decrease fall risk in older adults: study design of a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk. Methods/Design Three hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson’s disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function. Discussion This randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented

  11. Opinion formation in evaluating sanity at the time of the offense: an examination of 5175 pre-trial evaluations.

    PubMed

    Warren, Janet I; Murrie, Daniel C; Chauhan, Preeti; Dietz, Park E; Morris, James

    2004-01-01

    Sanity evaluations are high-stake undertakings that explicitly examine the defendant's culpability for a crime and implicitly explore clinical information that might inform a plea agreement. Despite the gravity of such evaluations, relatively little research has investigated the process by which evaluators form their psycholegal opinions. In the current study, we explore this process by examining 5175 sanity evaluations conducted by a cohort of forensic evaluators in Virginia over a ten-year period. Our analyses focus on (i) the clinical, criminal, and demographic attributes of the defendant correlated with opinions indicative of insanity; (ii) the clinical content of the evaluations and the legal criteria referenced as the basis for the psycholegal opinion; (iii) the process and outcome differences in the sanity evaluations conducted by psychologists versus psychiatrists; and (iv) the consistency in these opinions over a ten year period. Analyses predicting an opinion of insanity indicate a positive relationship with psychotic, organic, and affective diagnoses and previous psychiatric treatment. Analyses also indicate a negative relationship with prior criminal history, drug charges, personality disorder diagnosis, and intoxication at the time of the offense. Modest racial disparities were observed with evaluators offering opinions that the defendant was insane more often for white than for minority defendants despite comparable psychiatric and criminal characteristics.

  12. Reanalyses of the historical series of UK variety trials to quantify the contributions of genetic and environmental factors to trends and variability in yield over time.

    PubMed

    Mackay, I; Horwell, A; Garner, J; White, J; McKee, J; Philpott, H

    2011-01-01

    Historical datasets have much to offer. We analyse data from winter wheat, spring and winter barley, oil seed rape, sugar beet and forage maize from the UK National List and Recommended List trials over the period 1948-2007. We find that since 1982, for the cereal crops and oil seed rape, at least 88% of the improvement in yield is attributable to genetic improvement, with little evidence that changes in agronomy have improved yields. In contrast, in the same time period, plant breeding and changes in agronomy have contributed almost equally to increased yields of forage maize and sugar beet. For the cereals prior to 1982, contributions from plant breeding were 42, 60 and 86% for winter barley, winter wheat and spring barley, respectively. These results demonstrate the overwhelming importance of plant breeding in increasing crop productivity in the UK. Winter wheat data are analysed in more detail to exemplify the use of historical data series to study and detect disease resistance breakdown, sensitivity of varieties to climatic factors, and also to test methods of genomic selection. We show that breakdown of disease resistance can cause biased estimates of variety and year effects, but that comparison of results between fungicide treated and untreated trials over years may be a means to screen for durable resistance. We find the greatest sensitivities of the winter wheat germplasm to seasonal differences in rainfall and temperature are to summer rainfall and winter temperature. Finally, for genomic selection, correlations between observed and predicted yield ranged from 0.17 to 0.83. The high correlation resulted from markers predicting kinship amongst lines rather than tagging multiple QTL. We believe the full value of these data will come from exploiting links with other experiments and experimental populations. However, not to exploit such valuable historical datasets is wasteful.

  13. Tai chi qigong as a means to improve night-time sleep quality among older adults with cognitive impairment: a pilot randomized controlled trial

    PubMed Central

    Chan, Aileen WK; Yu, Doris SF; Choi, KC; Lee, Diana TF; Sit, Janet WH; Chan, Helen YL

    2016-01-01

    Purpose Age-related cognitivee decline is a growing public health concern worldwide. More than a quarter of adults with cognitive impairment experience sleep disturbance. The objective of this pilot study was to evaluate the preliminary effects of tai chi qigong (TCQ) on improving the night-time sleep quality of older adults with cognitive impairment. Participants Older adults with cognitive impairment who complain of sleep disturbance. Methods A randomized controlled trial with two groups. Fifty-two subjects were recruited from two district elderly community centers and randomly assigned to either the TCQ group (n=27) or the control group (n=25). The intervention group received TCQ training consisting of two 60-minute sessions each week for 2 months. The control group was advised to maintain their usual activities. Sleep quality was measured by the Chinese Pittsburgh Sleep Quality Index. Quality of life was measured by Short-form 12, cognitive functions measured by mini-mental state examination, and subjective memory deficits measured by the memory inventory for Chinese. Results Data were collected at baseline, 2 months, and 6 months. Significant results were noted at 6 months in the Chinese Pittsburgh Sleep Quality Index global score (P=0.004), sleep duration (P=0.003), habitual sleep efficiency (P=0.002), and the Short-form 12 mental health component (P<0.001). The TCQ participants reported better sleep quality and a better (quality of life) mental health component than the control group. Conclusion TCQ can be considered a useful nonpharmacological approach for improving sleep quality in older adults with cognitive impairment. Clinical trial registration CUHK_CCT00448 (https://www2.ccrb.cuhk.edu.hk/registry/public/287). PMID:27698557

  14. Tai chi qigong as a means to improve night-time sleep quality among older adults with cognitive impairment: a pilot randomized controlled trial

    PubMed Central

    Chan, Aileen WK; Yu, Doris SF; Choi, KC; Lee, Diana TF; Sit, Janet WH; Chan, Helen YL

    2016-01-01

    Purpose Age-related cognitivee decline is a growing public health concern worldwide. More than a quarter of adults with cognitive impairment experience sleep disturbance. The objective of this pilot study was to evaluate the preliminary effects of tai chi qigong (TCQ) on improving the night-time sleep quality of older adults with cognitive impairment. Participants Older adults with cognitive impairment who complain of sleep disturbance. Methods A randomized controlled trial with two groups. Fifty-two subjects were recruited from two district elderly community centers and randomly assigned to either the TCQ group (n=27) or the control group (n=25). The intervention group received TCQ training consisting of two 60-minute sessions each week for 2 months. The control group was advised to maintain their usual activities. Sleep quality was measured by the Chinese Pittsburgh Sleep Quality Index. Quality of life was measured by Short-form 12, cognitive functions measured by mini-mental state examination, and subjective memory deficits measured by the memory inventory for Chinese. Results Data were collected at baseline, 2 months, and 6 months. Significant results were noted at 6 months in the Chinese Pittsburgh Sleep Quality Index global score (P=0.004), sleep duration (P=0.003), habitual sleep efficiency (P=0.002), and the Short-form 12 mental health component (P<0.001). The TCQ participants reported better sleep quality and a better (quality of life) mental health component than the control group. Conclusion TCQ can be considered a useful nonpharmacological approach for improving sleep quality in older adults with cognitive impairment. Clinical trial registration CUHK_CCT00448 (https://www2.ccrb.cuhk.edu.hk/registry/public/287).

  15. Sub-Nyquist field trial using time frequency packed DP-QPSK super-channel within fixed ITU-T grid.

    PubMed

    Potì, L; Meloni, G; Berrettini, G; Fresi, F; Foggi, T; Secondini, M; Giorgi, L; Cavaliere, F; Hackett, S; Petronio, A; Nibbs, P; Forgan, R; Leong, A; Masciulli, R; Pfander, C

    2015-06-15

    Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super-channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR = 15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE∙d product of 9254 bit/s/Hz·km was achieved.

  16. Improved VO2max and time trial performance with more high aerobic intensity interval training and reduced training volume: a case study on an elite national cyclist.

    PubMed

    Støren, Øyvind; Bratland-Sanda, Solfrid; Haave, Marius; Helgerud, Jan

    2012-10-01

    The present study investigated to what extent more high aerobic intensity interval training (HAIT) and reduced training volume would influence maximal oxygen uptake (VO2max) and time trial (TT) performance in an elite national cyclist in the preseason period. The cyclist was tested for VO2max, cycling economy (C(c)), and TT performance on an ergometer cycle during 1 year. Training was continuously logged using heart rate monitor during the entire period. Total monthly training volume was reduced in the 2011 preseason compared with the 2010 preseason, and 2 HAIT blocks (14 sessions in 9 days and 15 sessions in 10 days) were performed as running. Between the HAIT blocks, 3 HAIT sessions per week were performed as cycling. From November 2010 to February 2011, the cyclist reduced total average monthly training volume by 18% and cycling training volume by 60%. The amount of training at 90-95% HRpeak increased by 41%. VO2max increased by 10.3% on ergometer cycle. TT performance improved by 14.9%. C(c) did not change. In conclusion, preseason reduced total training volume but increased amount of HAIT improved VO2max and TT performance without any changes in C(c). These improvements on cycling appeared despite that the HAIT blocks were performed as running. Reduced training time, and training transfer from running into improved cycling form, may be beneficial for cyclists living in cold climate areas.

  17. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

    PubMed

    Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

    2015-04-01

    Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

  18. Impairment of 40-km time-trial performance but not peak power output with external iliac kinking: a case study in a world-class cyclist.

    PubMed

    Lamberts, Robert P; Mann, T N; Rietjens, Gerard J; Tijdink, Hendrik H

    2014-07-01

    Iliac blood-flow restrictions causing painful and "powerless" legs are often attributed to overtraining and may develop for some time before being correctly diagnosed. In the current study, differences between actual performance parameters and performance parameters predicted from the Lamberts and Lambert Submaximal Cycle Test (LSCT) were studied in a world-class cyclist with bilateral kinking of the external iliac artery before and after surgery. Two performance-testing sessions, including a peak-power-output (PPO) test and a 40-km time trial (TT) were conducted before surgery, while 1 testing session was conducted after the surgery. Actual vs LSCT-predicted performance parameters in the world-class cyclists were compared with 82 symptom-free trained to elite male cyclists. No differences were found between actual and LSCT-predicted PPO before and after surgical intervention. However, there were differences between actual and LSCT-predicted 40-km TT time in the tests performed before the surgery (2:51and 2:55 min:s, respectively). These differences were no longer apparent in the postsurgery 40-km TT (2 s). This finding suggests that iliac blood-flow restrictions seem to mainly impair endurance performance rather than peak cycling performance. A standard PPO test without brachial ankle blood-pressure measurements might not be able to reflect iliac blood-flow restrictions. Differences between actual and LSCT-predicted 40-km TT time may assist in earlier referral to a cardiovascular specialist and result in earlier detection of iliac blood-flow restrictions.

  19. Physiological tolerance times while wearing explosive ordnance disposal protective clothing in simulated environmental extremes.

    PubMed

    Stewart, Ian B; Stewart, Kelly L; Worringham, Charles J; Costello, Joseph T

    2014-01-01

    Explosive ordnance disposal (EOD) technicians are required to wear protective clothing to protect themselves from the threat of overpressure, fragmentation, impact and heat. The engineering requirements to minimise these threats results in an extremely heavy and cumbersome clothing ensemble that increases the internal heat generation of the wearer, while the clothing's thermal properties reduce heat dissipation. This study aimed to evaluate the heat strain encountered wearing EOD protective clothing in simulated environmental extremes across a range of differing work intensities. Eight healthy males [age 25 ± 6 years (mean ± sd), height 180 ± 7 cm, body mass 79 ± 9 kg, VO2max 57 ± 6 ml(.) kg(-1.)min(-1)] undertook nine trials while wearing an EOD9 suit (weighing 33.4 kg). The trials involved walking on a treadmill at 2.5, 4 and 5.5 km ⋅ h(-1) at each of the following environmental conditions, 21, 30 and 37 °C wet bulb globe temperature (WBGT) in a randomised controlled crossover design. The trials were ceased if the participants' core temperature reached 39 °C, if heart rate exceeded 90% of maximum, if walking time reached 60 minutes or due to fatigue/nausea. Tolerance times ranged from 10-60 minutes and were significantly reduced in the higher walking speeds and environmental conditions. In a total of 15 trials (21%) participants completed 60 minutes of walking; however, this was predominantly at the slower walking speeds in the 21 °C WBGT environment. Of the remaining 57 trials, 50 were ceased, due to attainment of 90% maximal heart rate. These near maximal heart rates resulted in moderate-high levels of physiological strain in all trials, despite core temperature only reaching 39 °C in one of the 72 trials. PMID:24586228

  20. Assessment of arterial elasticity among HIV-positive participants with high CD4 cell counts: a substudy of the INSIGHT Strategic Timing of Anti Retroviral Treatment trial

    PubMed Central

    Baker, Jason V.; Engen, Nicole Wyman; Huppler Hullsiek, Katherine; Stephan, Christoph; Jain, Mamta K.; Munderi, Paula; Pett, Sarah; Duprez, Daniel

    2014-01-01

    Introduction Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function and structure can be used to study the pathogenesis and progression of CVD, including the effects of ART and other interventions. Methods We review available methods to assess vascular (dys)function and report our experience using analysis of the diastolic blood pressure (BP) waveform to estimate arterial elasticity among a subset of participants in the Strategic Timing of AntiRetroviral Treatment (START) trial. Linear regression was used to study cross-sectional associations between baseline clinical factors and small or large arterial elasticity. Results Arterial elasticity measurement was chosen for its improved measurement reproducibility over other methodologies and the potential of small arterial elasticity to predict clinical risk. Analysis of baseline data demonstrates that small artery elasticity is impaired (lower) with older age and differs by race and between geographic region. No HIV-specific factors studied remained significantly associated with arterial elasticity in multivariate models. Conclusion Longitudinal analyses in this substudy will provide essential randomised data to study the effects of early ART initiation on the progression of vascular disease among a diverse global population. When combined with future biomarker analyses and clinical outcomes in START, these findings will expand our understanding of the pathogenesis of HIV-related CVD. PMID:25711329

  1. fatalityCMR: capture-recapture software to correct raw counts of wildlife fatalities using trial experiments for carcass detection probability and persistence time

    USGS Publications Warehouse

    Peron, Guillaume; Hines, James E.

    2014-01-01

    Many industrial and agricultural activities involve wildlife fatalities by collision, poisoning or other involuntary harvest: wind turbines, highway network, utility network, tall structures, pesticides, etc. Impacted wildlife may benefit from official protection, including the requirement to monitor the impact. Carcass counts can often be conducted to quantify the number of fatalities, but they need to be corrected for carcass persistence time (removal by scavengers and decay) and detection probability (searcher efficiency). In this article we introduce a new piece of software that fits a superpopulation capture-recapture model to raw count data. It uses trial data to estimate detection and daily persistence probabilities. A recurrent issue is that fatalities of rare, protected species are infrequent, in which case the software offers the option to switch to an ‘evidence of absence’ mode, i.e., estimate the number of carcasses that may have been missed by field crews. The software allows distinguishing between different turbine types (e.g. different vegetation cover under turbines, or different technical properties), as well between two carcass age-classes or states, with transition between those classes (e.g, fresh and dry). There is a data simulation capacity that may be used at the planning stage to optimize sampling design. Resulting mortality estimates can be used 1) to quantify the required amount of compensation, 2) inform mortality projections for proposed development sites, and 3) inform decisions about management of existing sites.

  2. Trial Watch

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Hervé Fridman, Wolf; Cremer, Isabelle; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past 2 decades, the possibility that preparations capable of eliciting tumor-specific immune responses would mediate robust therapeutic effects in cancer patients has received renovated interest. In this context, several approaches to vaccinate cancer patients against their own malignancies have been conceived, including the administration of DNA constructs coding for one or more tumor-associated antigens (TAAs). Such DNA-based vaccines conceptually differ from other types of gene therapy in that they are not devised to directly kill cancer cells or sensitize them to the cytotoxic activity of a drug, but rather to elicit a tumor-specific immune response. In spite of an intense wave of preclinical development, the introduction of this immunotherapeutic paradigm into the clinical practice is facing difficulties. Indeed, while most DNA-based anticancer vaccines are well tolerated by cancer patients, they often fail to generate therapeutically relevant clinical responses. In this Trial Watch, we discuss the latest advances on the use of DNA-based vaccines in cancer therapy, discussing the literature that has been produced around this topic during the last 13 months as well as clinical studies that have been launched in the same time frame to assess the actual therapeutic potential of this intervention. PMID:24800178

  3. Quantitation of cytokine mRNA by real-time RT-PCR during a vaccination trial in a rabbit model of fascioliasis.

    PubMed

    Espino, Ana M; Rivera, Francheska

    2010-04-19

    Use of the rabbit as disease model has long been hampered by a lack of immunological assays specific to this species. In the present study we developed a SYBR Green-based, real-time RT-PCR protocol to quantitate cytokine mRNA in freshly harvested rabbit peripheral mononuclear cells. The method was validated in the course of a vaccination trial in which animals vaccinated with the recombinant antigen FhSAP2 were challenged with Fasciola hepatica metacercariae. Changes in the levels of rabbit interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) mRNA were determined. Messenger RNA from the universally expressed housekeeping gene GAPDH was used as an amplification control and allowed for correction of variations in the efficiencies of RNA extraction and reverse transcription. Rabbits vaccinated with FhSAP2 showed an 83.3% reduction in liver fluke burden after challenge infection when compared to non-vaccinated controls. All cytokine mRNAs were found at detectable levels; however, the levels of IFNgamma, TNFalpha, IL-2 and IL-10 were significantly higher in the vaccinated group compared to the non-vaccinated group. These results suggest that protection conferred by FhSAP2 protein could be associated with a mixed Th1/Th2 immune response in which Th1 cytokines are dominant. The real-time RT-PCR method described herein can be a useful tool for monitoring changes in basic immune functions in the rabbit model of fascioliasis and may also aid in studies of human diseases for which the rabbit is an important experimental model. PMID:20056331

  4. Clinical Trials

    MedlinePlus

    ... of visits, and any adjustments to treatment. (back) Requirements for Participation Admission into a clinical trial is based on a rigid set of requirements. You must be diagnosed with the illness that ...

  5. 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.

    PubMed

    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.

  6. Real-time monitoring of railway infrastructures using fibre Bragg grating sensors

    NASA Astrophysics Data System (ADS)

    Roveri, N.; Carcaterra, A.; Sestieri, A.

    2015-08-01

    In this work we present the results of a field trial with a FBG sensor array system for the real time monitoring of railway traffic and for the structural health monitoring of both the railway track and train wheels. The test campaign is performed on the 2nd line of Milan metropolitan underground, employing more than 50 FBG sensors along 1.5 km of the rail track, where the trains are tested during daily passenger rail transport, with a roughly maximum speeds of 90 km/h. The measurements were continuatively performed for over 6 months, with a sampling frequency of about 400 Hz. The large amount of data/sensors allows a rather accurate statistical treatment of the measurement data and permits, with dedicated algorithms, the estimation of rail and wheel wear, key traffic parameters such as the number of axles, the train speed and load, and, in the next future, the detection of localized imperfections.

  7. A placebo-controlled, double-blind clinical trial to evaluate the efficacy of Imedeen® Time Perfection® for improving the appearance of photodamaged skin

    PubMed Central

    Stephens, Thomas J; Sigler, Monya L; Herndon, James H; Dispensa, Lisa; Le Moigne, Anne

    2016-01-01

    Objective To assess the efficacy of Imedeen Time Perfection for improving the appearance and condition of photoaged skin in healthy women. Methods This randomized, double-blind, placebo-controlled clinical trial enrolled healthy women, 35–60 years of age, with Fitzpatrick I–III and Glogau II–III skin types and mild-to-moderate facial fine lines/wrinkles. The eligible subjects were randomized to receive two tablets daily of either Imedeen Time Perfection (Imedeen) or a matching placebo for 12 weeks. Efficacy assessments included investigator rating of 16 photoaging parameters (ie, global facial appearance and 15 individual facial parameters and the average of all parameters), instrumentation (ie, ultrasound dermal density, moisture level of the stratum corneum, transepidermal water loss, cutometry), and subjects’ self-assessment. Differences in the mean change from baseline to week 12 values on these outcomes were compared between Imedeen and placebo using analysis of variance or a paired t-test. Results Seventy-four subjects with primarily Fitzpatrick skin type III (78%–79%) and Glogau type III (53%–58%) completed the study (Imedeen: n=36; placebo: n=38). The mean difference in change from baseline to week 12 for global facial assessment significantly favored Imedeen over placebo (−0.52; P=0.0017). Additionally, the mean differences in the average of all facial photoaging parameters (−0.29), mottled hyperpigmentation (−0.25), tactile laxity (−0.24), dullness (−0.47), and tactile roughness (−0.62) significantly favored Imedeen over placebo (P≤0.05). Significantly greater increases in ultrasound dermal density (+11% vs +1%; P≤0.05) and stratum corneum moisturization (+30% vs +6%; P≤0.05) were also observed for Imedeen than for placebo. There were no significant differences on other instrumental outcomes. Conclusion The results of this study suggest that Imedeen Time Perfection can positively affect the appearance of photoaged skin

  8. Fluid therapy LiDCO controlled trial-optimization of volume resuscitation of extensively burned patients through noninvasive continuous real-time hemodynamic monitoring LiDCO.

    PubMed

    Tokarik, Monika; Sjöberg, Folke; Balik, Martin; Pafcuga, Igor; Broz, Ludomir

    2013-01-01

    This pilot trial aims at gaining support for the optimization of acute burn resuscitation through noninvasive continuous real-time hemodynamic monitoring using arterial pulse contour analysis. A group of 21 burned patients meeting preliminary criteria (age range 18-75 years with second- third- degree burns and TBSA ≥10-75%) was randomized during 2010. A hemodynamic monitoring through lithium dilution cardiac output was used in 10 randomized patients (LiDCO group), whereas those without LiDCO monitoring were defined as the control group. The modified Brooke/Parkland formula as a starting resuscitative formula, balanced crystalloids as the initial solutions, urine output of 0.5 ml/kg/hr as a crucial value of adequate intravascular filling were used in both groups. Additionally, the volume and vasopressor/inotropic support were based on dynamic preload parameters in the LiDCO group in the case of circulatory instability and oligouria. Statistical analysis was done using t-tests. Within the first 24 hours postburn, a significantly lower consumption of crystalloids was registered in LiDCO group (P = .04). The fluid balance under LiDCO control in combination with hourly diuresis contributed to reducing the cumulative fluid balance approximately by 10% compared with fluid management based on standard monitoring parameters. The amount of applied solutions in the LiDCO group got closer to Brooke formula whereas the urine output was at the same level in both groups (0.8 ml/kg/hr). The new finding in this study is that when a fluid resuscitation is based on the arterial waveform analysis, the initial fluid volume provided was significantly lower than that delivered on the basis of physician-directed fluid resuscitation (by urine output and mean arterial pressure).

  9. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    SciTech Connect

    Obeid, L; Esteve, F; Adam, J; Tessier, A; Balosso, J

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  10. 'Mind the Gap'-The Impact of Variations in the Duration of the Treatment Gap and Overall Treatment Time in the First UK Anal Cancer Trial (ACT I)

    SciTech Connect

    Glynne-Jones, Rob; Sebag-Montefiore, David; Adams, Richard; McDonald, Alec; Gollins, Simon; James, Roger; Northover, John M.A.; Meadows, Helen M.; Jitlal, Mark

    2011-12-01

    Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

  11. Trial Watch

    PubMed Central

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

  12. [Time-dependent confounding in the estimation of treatment effects in randomised trials with multimodal therapies--an illustration of the problem of time-dependent confounding by causal graphs].

    PubMed

    Zietemann, V D; Schuster, T; Duell, T H G

    2015-01-01

    Biased effect estimates induced by unconsidered confounding variables are a known problem in observational studies. Selection bias, resulting from non-random sampling of study participants, is widely recognised as a problem in case-control and cross-sectional studies. In contrast, possible bias in randomised controlled trials (RCTs) is mostly ignored. This paper illustrates, by applying directed acyclic graphs (DAGs), possible bias in the effect estimates of first-line therapy, caused by subsequent changes in therapy (time-dependent confounding). Possible selection bias, induced by not only random loss to follow-up, will be explained as well using DAGs. Underlying assumptions of standard methods usually used to analyse RCTs (like intention-to-treat, per-protocol) are shown and it is explained why effect estimates may be biased in RCTs, if only these conventional methods are used. Adequate statistical methods (causal inference models as marginal structural models and structural nested models) exist. Higher documentary efforts, however, are necessary, because any changes in medication, loss to follow-up as well as reasons for such changes need to be documented in detail as required by these advanced statistical methods. Nevertheless, causal inference models should become standard along side the currently applied standard methods, especially in studies with high non-compliance due to changes in therapy and substantial loss to follow-up. Possible bias cannot be excluded if similar results are obtained from both methods. However, study results should be interpreted with caution if they differ between both approaches.

  13. Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial

    PubMed Central

    Robling, Michael; Bekkers, Marie-Jet; Bell, Kerry; Butler, Christopher C; Cannings-John, Rebecca; Channon, Sue; Martin, Belen Corbacho; Gregory, John W; Hood, Kerry; Kemp, Alison; Kenkre, Joyce; Montgomery, Alan A; Moody, Gwenllian; Owen-Jones, Eleri; Pickett, Kate; Richardson, Gerry; Roberts, Zoë E S; Ronaldson, Sarah; Sanders, Julia; Stamuli, Eugena; Torgerson, David

    2016-01-01

    Summary Background Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. Methods We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. Findings Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823

  14. The effectiveness and cost-effectiveness of the Family Nurse Partnership home visiting programme for first time teenage mothers in England: a protocol for the Building Blocks randomised controlled trial

    PubMed Central

    2013-01-01

    Background The Nurse Family Partnership programme was developed in the USA where it is made available to pregnant young mothers in some socially deprived geographic areas. The related Family Nurse Partnership programme was introduced in England by the Department of Health in 2006 with the aim of improving outcomes for the health, wellbeing and social circumstances of young first-time mothers and their children. Methods / design This multi-centre individually randomised controlled trial will recruit 1600 participants from 18 Primary Care Trusts in England, United Kingdom. The trial will evaluate the effectiveness of Family Nurse Partnership programme and usual care versus usual care for nulliparous pregnant women aged 19 or under, recruited by 24 weeks gestation and followed until the child’s second birthday. Data will be collected from participants at baseline, 34-36 weeks gestation, 6, 12, 18 and 24 months following birth. Routine clinical data will be collected from maternity, primary care and hospital episodes statistics. Four primary outcomes are to be reported from the trial: birth weight; prenatal tobacco use; child emergency attendances and/or admissions within two years of birth; second pregnancy within two years of first birth. Discussion This trial will evaluate the effectiveness and cost effectiveness of the Family Nurse Partnership in England. The findings will provide evidence on pregnancy and early childhood programme outcomes for policy makers, health professionals and potential recipients in three domains (pregnancy and birth, child health and development, and parental life course and self-sufficiency) up to the child’s second birthday. Trial registration Trial registration number: ISRCTN 23019866 PMID:23919573

  15. The impact of frequency of patient self-testing of prothrombin time on time in target range within VA Cooperative Study #481: The Home INR Study (THINRS), a randomized, controlled trial.

    PubMed

    Matchar, David B; Love, Sean R; Jacobson, Alan K; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Dolor, Rowena J

    2015-07-01

    Anticoagulation (AC) is effective in reducing thromboembolic events for individuals with atrial fibrillation (AF) or mechanical heart valve (MHV), but maintaining patients in target range for international normalized ratio (INR) can be difficult. Evidence suggests increasing INR testing frequency can improve time in target range (TTR), but this can be impractical with in-clinic testing. The objective of this study was to test the hypothesis that more frequent patient-self testing (PST) via home monitoring increases TTR. This planned substudy was conducted as part of The Home INR Study, a randomized controlled trial of in-clinic INR testing every 4 weeks versus PST at three different intervals. The setting for this study was 6 VA centers across the United States. 1,029 candidates with AF or MHV were trained and tested for competency using ProTime INR meters; 787 patients were deemed competent and, after second consent, randomized across four arms: high quality AC management (HQACM) in a dedicated clinic, with venous INR testing once every 4 weeks; and telephone monitored PST once every 4 weeks; weekly; and twice weekly. The primary endpoint was TTR at 1-year follow-up. The secondary endpoints were: major bleed, stroke and death, and quality of life. Results showed that TTR increased as testing frequency increased (59.9 ± 16.7 %, 63.3 ± 14.3 %, and 66.8 ± 13.2 % [mean ± SD] for the groups that underwent PST every 4 weeks, weekly and twice weekly, respectively). The proportion of poorly managed patients (i.e., TTR <50 %) was significantly lower for groups that underwent PST versus HQACM, and the proportion decreased as testing frequency increased. Patients and their care providers were unblinded given the nature of PST and HQACM. In conclusion, more frequent PST improved TTR and reduced the proportion of poorly managed patients.

  16. Time?

    NASA Astrophysics Data System (ADS)

    Amoroso, Richard L.

    2013-09-01

    The concept of time in the `clockwork' Newtonian world was irrelevant; and has generally been ignored until recently by several generations of physicists since the implementation of quantum mechanics. We will set aside the utility of time as a property relating to physical calculations of events relating to a metrics line element or as an aspect of the transformation of a particles motion/interaction in a coordinate system or in relation to thermodynamics etc., i.e. we will discard all the usual uses of time as a concept used to circularly define physical parameters in terms of other physical parameters; concentrating instead on time as an aspect of the fundamental cosmic topology of our virtual reality especially as it inseparably relates to the nature and role of the observer in natural science.

  17. Social Problem Solving and Depressive Symptoms over Time: A Randomized Clinical Trial of Cognitive-Behavioral Analysis System of Psychotherapy, Brief Supportive Psychotherapy, and Pharmacotherapy

    ERIC Educational Resources Information Center

    Klein, Daniel N.; Leon, Andrew C.; Li, Chunshan; D'Zurilla, Thomas J.; Black, Sarah R.; Vivian, Dina; Dowling, Frank; Arnow, Bruce A.; Manber, Rachel; Markowitz, John C.; Kocsis, James H.

    2011-01-01

    Objective: Depression is associated with poor social problem solving, and psychotherapies that focus on problem-solving skills are efficacious in treating depression. We examined the associations between treatment, social problem solving, and depression in a randomized clinical trial testing the efficacy of psychotherapy augmentation for…

  18. Critical power derived from a 3-min all-out test predicts 16.1-km road time-trial performance.

    PubMed

    Black, Matthew I; Durant, Jacob; Jones, Andrew M; Vanhatalo, Anni

    2014-01-01

    It has been shown that the critical power (CP) in cycling estimated using a novel 3-min all-out protocol is reliable and closely matches the CP derived from conventional procedures. The purpose of this study was to assess the predictive validity of the all-out test CP estimate. We hypothesised that the all-out test CP would be significantly correlated with 16.1-km road time-trial (TT) performance and more strongly correlated with performance than the gas exchange threshold (GET), respiratory compensation point (RCP) and VO2 max. Ten club-level male cyclists (mean±SD: age 33.8±8.2 y, body mass 73.8±4.3 kg, VO2 max 60±4 ml·kg(-1)·min(-1)) performed a 10-mile road TT, a ramp incremental test to exhaustion, and two 3-min all-out tests, the first of which served as familiarisation. The 16.1-km TT performance (27.1±1.2 min) was significantly correlated with the CP (309±34 W; r = -0.83, P<0.01) and total work done during the all-out test (70.9±6.5 kJ; r = -0.86, P<0.01), the ramp incremental test peak power (433±30 W; r = -0.75, P<0.05) and the RCP (315±29 W; r = -0.68, P<0.05), but not with GET (151±32 W; r = -0.21) or the VO2 max (4.41±0.25 L·min(-1); r = -0.60). These data provide evidence for the predictive validity and practical performance relevance of the 3-min all-out test. The 3-min all-out test CP may represent a useful addition to the battery of tests employed by applied sport physiologists or coaches to track fitness and predict performance in atheletes.

  19. Assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: study protocol for an individual participant data meta-analysis of randomised controlled trials

    PubMed Central

    Voysey, Merryn; Pollard, Andrew J; Perera, Rafael; Fanshawe, Thomas R

    2016-01-01

    Introduction Disease incidence differs between males and females for some infectious or inflammatory diseases. Sex-differences in immune responses to some vaccines have also been observed, mostly to viral vaccines in adults. Little evidence is available on whether sex-differences occur in response to immunisation in infancy even though this is the age group in which most vaccines are administered. Factors other than sex, such as timing or coadministration of other vaccines, can also influence the immune response to vaccination. Methods and analysis Individual participant data meta-analysis of randomised controlled trials of vaccines in healthy infants and young children will be conducted. Fully anonymised data from ∼170 randomised controlled trials of vaccines for diphtheria, tetanus, Bordetella pertussis, polio, Haemophilus influenzae type B, hepatitis B, Streptococcus pneumoniae, Neisseria meningitidis, measles, mumps, rubella, varicella and rotavirus will be combined for analysis. Outcomes include measures of immunogenicity (immunoglobulins), reactogenicity, safety and disease-specific clinical efficacy. Data from trials of vaccines containing similar components will be combined in hierarchical models and the effect of sex and timing of vaccinations estimated for each outcome separately. Ethics and dissemination Systematic reviews of published estimates of sex-differences cannot adequately answer questions in this field since such comparisons are never the main purpose of a clinical trial, thus a large degree of reporting bias exists in the published literature. Recent improvements in the widespread availability of individual participant data from randomised controlled trials makes it feasible to conduct extensive individual participant data meta-analyses which were previously impossible, thereby reducing the effect of publication or reporting bias on the understanding of the infant immune response. Preliminary results will be available in 2016 with final

  20. Clinical trials

    PubMed Central

    Garnham, J. C.

    1974-01-01

    The choice of standard drugs to be used in clinical trials must be based on consideration of human absorption data, in vitro characteristics, possible interactions, comparative efficacy and safety, previous data regarding the standard in relation to the syndrome to be studied, and correlation of blood levels, effectiveness and safety. PMID:4465771

  1. Bayesian Clinical Trials in Action

    PubMed Central

    Lee, J. Jack; Chu, Caleb T.

    2012-01-01

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. The alternative Bayesian paradigm has been greatly enhanced by advancements in computational algorithms and computer hardware. Compared to its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and for studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation, and analysis, and Web-based applications, which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More such trials should be designed and conducted to refine the approach and demonstrate its real benefit in action. PMID:22711340

  2. Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial

    PubMed Central

    Palvai, Sreekanth; Harrison, Michael; Shibu Thomas, Sharon; Hayden, Karen; Green, James; Anderson, Oliver; Romero, Lavinia; Lodge, Richard; Burns, Patricia

    2015-01-01

    Background Prostate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT. Objective Assessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile. Methods Timing of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity

  3. Time to be BRAVE: is educating surgeons the key to unlocking the potential of randomised clinical trials in surgery? A qualitative study

    PubMed Central

    2014-01-01

    Background Well-designed randomised clinical trials (RCTs) provide the best evidence to inform decision-making and should be the default option for evaluating surgical procedures. Such trials can be challenging, and surgeons’ preferences may influence whether trials are initiated and successfully conducted and their results accepted. Preferences are particularly problematic when surgeons’ views play a key role in procedure selection and patient eligibility. The bases of such preferences have rarely been explored. Our aim in this qualitative study was to investigate surgeons’ preferences regarding the feasibility of surgical RCTs and their understanding of study design issues using breast reconstruction surgery as a case study. Methods Semistructured qualitative interviews were undertaken with a purposive sample of 35 professionals practicing at 15 centres across the United Kingdom. Interviews were transcribed verbatim and analysed thematically using constant comparative techniques. Sampling, data collection and analysis were conducted concurrently and iteratively until data saturation was achieved. Results Surgeons often struggle with the concept of equipoise. We found that if surgeons did not feel ‘in equipoise’, they did not accept randomisation as a method of treatment allocation. The underlying reasons for limited equipoise were limited appreciation of the methodological weaknesses of data derived from nonrandomised studies and little understanding of pragmatic trial design. Their belief in the value of RCTs for generating high-quality data to change or inform practice was not widely held. Conclusion There is a need to help surgeons understand evidence, equipoise and bias. Current National Institute of Health Research/Medical Research Council investment into education and infrastructure for RCTs, combined with strong leadership, may begin to address these issues or more specific interventions may be required. PMID:24628821

  4. Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

    2015-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

  5. Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

    PubMed Central

    Mac Kenzie, William R.; Heilig, Charles M.; Bozeman, Lorna; Johnson, John L.; Muzanye, Grace; Dunbar, Denise; Jost, Kenneth C.; Diem, Lois; Metchock, Beverly; Eisenach, Kathleen; Dorman, Susan; Goldberg, Stefan

    2011-01-01

    Background Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. Methods In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. Results African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. Conclusions Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory

  6. Trial Watch

    PubMed Central

    Galluzzi, Lorenzo; Vacchelli, Erika; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zucman-Rossi, Jessica; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Since the advent of hybridoma technology, dating back to 1975, monoclonal antibodies have become an irreplaceable diagnostic and therapeutic tool for a wide array of human diseases. During the last 15 years, several monoclonal antibodies (mAbs) have been approved by FDA for cancer therapy. These mAbs are designed to (1) activate the immune system against tumor cells, (2) inhibit cancer cell-intrinsic signaling pathways, (3) bring toxins in the close proximity of cancer cells, or (4) interfere with the tumor-stroma interaction. More recently, major efforts have been made for the development of immunostimulatory mAbs that either enhance cancer-directed immune responses or limit tumor- (or therapy-) driven immunosuppression. Some of these antibodies, which are thought to facilitate tumor eradication by initiating or sustaining a tumor-specific immune response, have already entered clinical trials. In this Trial Watch, we will review and discuss the clinical progress of the most important mAbs that are have entered clinical trials after January 2008. PMID:22720209

  7. Trial Watch

    PubMed Central

    Vacchelli, Erika; Aranda, Fernando; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Cremer, Isabelle; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Accumulating evidence suggests that the clinical efficacy of selected anticancer drugs, including conventional chemotherapeutics as well as targeted anticancer agents, originates (at least in part) from their ability to elicit a novel or reinstate a pre-existing tumor-specific immune response. One of the mechanisms whereby chemotherapy can stimulate the immune system to recognize and destroy malignant cells is commonly known as immunogenic cell death (ICD). Cancer cells succumbing to ICD are de facto converted into an anticancer vaccine and as such elicit an adaptive immune response. Several common chemotherapeutics share the ability of triggering ICD, as demonstrated in vaccination experiments relying on immunocompetent mice and syngeneic cancer cells. A large number of ongoing clinical trials involve such ICD inducers, often (but not always) as they are part of the gold standard therapeutic approach against specific neoplasms. In this Trial Watch, we summarize the latest advances on the use of cyclophosphamide, doxorubicin, epirubicin, oxaliplatin, and mitoxantrone in cancer patients, discussing high-impact studies that have been published during the last 13 months as well as clinical trials that have been initiated in the same period to assess the antineoplastic profile of these immunogenic drugs as off-label therapeutic interventions. PMID:24800173

  8. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Hervé Fridman, Wolf; Cremer, Isabelle; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    The expression “adoptive cell transfer” (ACT) is commonly employed to indicate an immunotherapeutic regimen involving the isolation of autologous blood-borne or tumor-infiltrating lymphocytes, their selection/expansion/activation ex vivo, and their reinfusion into the patient, most often in the context of lymphodepleting pre-conditioning and in combination with immunostimulatory treatments. Optionally, the cellular material for ACT is genetically manipulated before expansion to (1) target specific tumor-associated antigens; (2) endogenously express immunostimulatory molecules; and/or (3) persist for long periods upon reinfusion. Consistent efforts have been dedicated at the amelioration of this immunotherapeutic regimen throughout the past decade, resulting in the establishment of ever more efficient and safer ACT protocols. Accordingly, the number of clinical trials testing ACT in oncological indications does not cease to increase. In this Trial Watch, we summarize recent developments in this exciting area of research, covering both high-impact studies that have been published during the last 12 months and clinical trials that have been launched in the same period to evaluate the safety and therapeutic potential of ACT in cancer patients. PMID:25050207

  9. Participating in Clinical Trials

    MedlinePlus

    ... this page please turn Javascript on. Participating in Clinical Trials About Clinical Trials A Research Study With Human Subjects A clinical ... to treat or cure a disease. Phases of Clinical Trials Clinical trials of drugs are usually described based ...

  10. Redesigning TRACER trial after TRITON.

    PubMed

    Serebruany, Victor L

    2015-10-15

    Designing of smart clinical trials is critical for regulatory approval and future drug utilization. Importantly, trial design should be reconsidered if the interim analyses suggest unexpected harm, or conflicting results were yielded from the other trials within the same therapeutic area. With regard to antiplatelet agents, the perfect example is redesigning of the ongoing PRoFESS trial by eliminating aspirin from clopidogrel arm after the earlier MATCH trial results became available. The goal was to aseess the unchanged TRACER trial design in light of the evidence yielded from the earlier completed TRITON trial. TRACER was designed as a triple versus dual antiplatelet trial in NSTEMI patients with no previous long-term outcome data supporting such aggressive strategy. TRITON data represented dual versus dual antiplatelet therapy, and became available before TRACER enrollment starts revealing prasugrel front-loaded early vascular benefit predominantly in STEMI patients with the growing over time bleeding and cancer risks. Moreover, large prasugrel NSTEMI TRITON cohort exhibited trend towards excess mortality in experimental arm warning against aggressive TRACER design. The long-term TRITON results in general, and especially in the NSTEMI patients challenge unchanged TRACER trial design. Applying dual, rather than triple antiplatelet therapy protocol modification should be considered in TRACER to minimize bleeding, cancer, and non-cardiovascular death risks. PMID:26126053

  11. Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

    SciTech Connect

    Gondi, Vinai; Cui, Yunfeng; Mehta, Minesh P.; Manfredi, Denise; Xiao, Ying; Galvin, James M.; Rowley, Howard; Tome, Wolfgang A.

    2015-03-01

    Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the

  12. Trial watch

    PubMed Central

    Galluzzi, Lorenzo; Senovilla, Laura; Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond to DC-based anticancer vaccines. This knowledge may indeed lead to personalized combination strategies that would extend the benefit of DC-based immunotherapy to a larger patient population. In addition, widespread enthusiasm has been generated by the results of the first clinical trials based on in vivo DC targeting, an approach that holds great promises for the future of DC-based immunotherapy. In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating DC-based interventions for cancer therapy. PMID:23170259

  13. What can we learn from the time course of untreated and partially treated community-onset Streptococcus pneumoniae pneumonia? A clinical perspective on superiority and noninferiority trial designs for mild community-acquired pneumonia.

    PubMed

    File, Thomas M; Schentag, Jerome J

    2008-12-01

    There are no well-designed placebo-controlled clinical trials in the recent era that precisely define the magnitude of the drug effect of antimicrobial therapy for mild community-acquired pneumonia (CAP). However, there is evidence that ineffective therapies, selected on the basis of the ratio of 24-h area under the concentration curve to minimum inhibitory concentration, associated with a discordant (nonsusceptible in vitro) specific agent (or no therapy) for mild CAP due to Streptococcus pneumoniae are associated with increased risk of progression to serious CAP. The relatively high rate of clinical success associated with appropriate antimicrobial treatment of mild CAP renders a standard outcome measure of clinical success an unlikely way to differentiate new agents. However, there may be an advantage in composite outcome assessments for mild CAP. Composite-outcomes end points that include time to resolution of morbidity, the use of patient reported-outcomes instruments, and biomarkers are recommended for future studies. Because the composite rate of success in recent randomized clinical trials exceeds 90%, it would seem that a noninferiority margin of 10% is reasonable for trials for mild CAP.

  14. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Fridman, Wolf Hervé; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a PD-1-targeting mAb formerly known as BMS-936558. Accordingly, the safety and efficacy of nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents. PMID:24701370

  15. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Cremer, Isabelle; Henrik ter Meulen, Jan; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic. PMID:25083332

  16. Trial watch

    PubMed Central

    Vacchelli, Erika; Galluzzi, Lorenzo; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Toll-like receptors (TLRs) have first been characterized for their capacity to detect conserved microbial components like lipopolysaccharide (LPS) and double-stranded RNA, resulting in the elicitation of potent (innate) immune responses against invading pathogens. More recently, TLRs have also been shown to promote the activation of the cognate immune system against cancer cells. Today, only three TLR agonists are approved by FDA for use in humans: the bacillus Calmette-Guérin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis, but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from the LPS of Salmonella minnesota) is included in the formulation of Cervarix®, a vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic imidazoquinoline) is routinely employed for actinic keratosis, superficial basal cell carcinoma, and external genital warts (condylomata acuminata). In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating FDA-approved TLR agonists as off-label medications for cancer therapy. PMID:23162757

  17. Timing of Chemotherapy After MammoSite Radiation Therapy System Breast Brachytherapy: Analysis of the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial

    SciTech Connect

    Haffty, Bruce G. Vicini, Frank A.; Beitsch, Peter; Quiet, Coral; Keleher, Angela; Garcia, Delia; Snider, Howard; Gittleman, Mark; Zannis, Victor; Kuerer, Henry; Whitacre, Eric; Whitworth, Pat; Fine, Richard; Keisch, Martin

    2008-12-01

    Purpose: To evaluate cosmetic outcome and radiation recall in the American Society of Breast Surgeons registry trial, as a function of the interval between accelerated partial breast irradiation (APBI) and initiation of chemotherapy (CTX). Methods and Materials: A total of 1440 patients at 97 institutions participated in this trial. After lumpectomy for early-stage breast cancer, patients received APBI (34 Gy in 10 fractions) with MammoSite RTS brachytherapy. A total of 148 patients received CTX within 90 days of APBI. Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. Results: Chemotherapy was initiated at a mean of 3.9 weeks after the final MammoSite procedure and was administered {<=}3 weeks after APBI in 54 patients (36%) and >3 weeks after APBI in 94 patients (64%). The early and delayed groups were well balanced with respect to multiple factors that may impact on cosmetic outcome. There was a superior cosmetic outcome in those receiving chemotherapy >3 weeks after APBI (excellent/good in 72.2% at {<=}3 weeks vs. excellent/good in 93.8% at >3 weeks; p = 0.01). Radiation recall in those receiving CTX at {<=}3 weeks was 9 of 50 (18%), compared with 6 of 81(7.4%) in those receiving chemotherapy at >3 weeks (p = 0.09). Conclusion: The majority of patients receiving CTX after APBI have excellent/good cosmetic outcomes, with a low rate of radiation recall. Chemotherapy initiated >3 weeks after the final MammoSite procedure seems to be associated with a better cosmetic outcome and lower rate of radiation recall. An excellent/good cosmetic outcome in patients receiving CTX after 3 weeks was similar to the cosmetic outcome of the overall patient population who did not receive CTX.

  18. Novelty causes time-dependent retrograde amnesia for one-trial avoidance in rats through NMDA receptor- and CaMKII-dependent mechanisms in the hippocampus.

    PubMed

    Izquierdo, I; Schröder, N; Netto, C A; Medina, J H

    1999-09-01

    Exposure to a novel environment (an open field) for 2 min, 1 h after one-trial inhibitory avoidance training, hindered memory of the avoidance task measured 24 h later. The effect was seen regardless of the intensity of the avoidance training footshock. The effect was not seen if the exposure to novelty was carried out 5 min before, or 6 h after, the avoidance training, or if the animals did not perceive the open field as new and react accordingly. The amnesic effect of the novelty presented 1 h after avoidance training was blocked by the intrahippocampal infusion of D-2-amino-5-phosphono-pentanoic acid (AP5, 25 nmoles per side) or 1-(N, O-bis-[5-isoquinolinylsulphonyl]-N-methyl-L-tyrosyl)-4- phenylpiperazine (KN62, 100 micromoles per side) but not by that of C32H25N3O6 (KT5720, 90 micromoles per side) given 5 min before the novelty. In the open field there was habituation, measured by the decrease in exploration between the first and second minute. AP5 and KN62 impaired this habituation, but not KT5720. Exploration of the open field was similar in the groups exposed to the avoidance task 5 min later, or 1 h or 6 h before. Therefore, there was no reciprocity between the effect of the two tasks: novelty was amnesic for the one-trial avoidance task, but the opposite was not true. The amnesic effect of novelty appears to rely on N-methyl-D-aspartate (NMDA) receptor- and calcium/calmodulin-dependent protein kinase II (CaMKII)-dependent, but not on PKA-dependent, aspects of its habituation learning.

  19. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  20. Classical swine fever virus detection: results of a real-time reverse transcription polymerase chain reaction ring trial conducted in the framework of the European network of excellence for epizootic disease diagnosis and control.

    PubMed

    Hoffmann, Bernd; Blome, Sandra; Bonilauri, Paolo; Fernández-Piñero, Jovita; Greiser-Wilke, Irene; Haegeman, Andy; Isaksson, Mats; Koenen, Frank; LeBlanc, Neil; Leifer, Immanuel; Le Potier, Marie-Frederique; Loeffen, Willie; Rasmussen, Thomas Bruun; Stadejek, Tomasz; Ståhl, Karl; Tignon, Marylène; Uttenthal, Ase; van der Poel, Wim; Beer, Martin

    2011-09-01

    The current study reports on a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) ring trial for the detection of Classical swine fever virus (CSFV) genomic RNA undertaken by 10 European laboratories. All laboratories were asked to use their routine in-house real-time RT-PCR protocols and a standardized protocol commonly used by the Friedrich-Loeffler-Institute (FLI) on a panel of well-characterized samples. In general, all participants produced results within the acceptable range. The FLI assay, several in-house assays, and the commercial kits had high analytical sensitivity and specificity values. Nevertheless, some in-house systems had unspecific reactions or suboptimal sensitivity with only a single CSFV genotype. Follow-up actions involved either improvement of suboptimal assays or replacement of specific laboratory assays with the FLI protocol, with or without modifications. In conclusion, the ring trial showed reliability of classical swine fever diagnosis on an international level and helped to optimize CSFV-specific RT-PCR diagnostics.

  1. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    During the past two decades, the notion that cancer would merely constitute a cell-intrinsic disease has gradually been complemented by a model postulating that the immune system plays a relevant role during all stages of oncogenesis and tumor progression. Along with this conceptual shift, several strategies have been devised to stimulate tumor-specific immune responses, including relatively unselective approaches such as the systemic administration of adjuvants or immunomodulatory cytokines. One year ago, in the July issue of OncoImmunology, we described the main biological features of this large group of proteins and discussed the progress of ongoing clinical studies evaluating their safety and therapeutic potential in cancer patients. Here, we summarize the latest developments in this area of clinical research, focusing on high impact studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate which cytokines can be employed as safe and efficient immunostimulatory interventions against cancer. PMID:24073369

  2. Trial watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term “oncolytic viruses” is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called “oncotropic viruses” in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of oncolytic virotherapy. PMID:23894720

  3. Trial watch

    PubMed Central

    Vacchelli, Erika; Vitale, Ilio; Eggermont, Alexander; Fridman, Wolf Hervé; Fučíková, Jitka; Cremer, Isabelle; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological tolerance, mature DCs are capable of priming robust, and hence therapeutically relevant, adaptive immune responses. In line with this notion, functional defects in the DC compartment have been shown to etiologically contribute to pathological conditions including (but perhaps not limited to) infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. Thus, the possibility of harnessing the elevated immunological potential of DCs for anticancer therapy has attracted considerable interest from both researchers and clinicians over the last decade. Alongside, several methods have been developed not only to isolate DCs from cancer patients, expand them, load them with tumor-associated antigens and hence generate highly immunogenic clinical grade infusion products, but also to directly target DCs in vivo. This intense experimental effort has culminated in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T, Provenge®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer. As an update to the latest Trial Watch dealing with this exciting field of research (October 2012), here we summarize recent advances in DC-based anticancer regimens, covering both high-impact studies that have been published during the last 13 mo and clinical trials that have been launched in the same period to assess the antineoplastic potential of this variant of cellular immunotherapy. PMID:24286020

  4. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy. PMID:23762803

  5. How transparent are migraine clinical trials?

    PubMed Central

    Dufka, Faustine L.; Dworkin, Robert H.

    2014-01-01

    Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

  6. How Do Clinical Trials Work?

    MedlinePlus

    ... Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  7. Pipeline Decommissioning Trial AWE Berkshire UK - 13619

    SciTech Connect

    Agnew, Kieran

    2013-07-01

    This Paper details the implementation of a 'Decommissioning Trial' to assess the feasibility of decommissioning the redundant pipeline operated by AWE located in Berkshire UK. The paper also presents the tool box of decommissioning techniques that were developed during the decommissioning trial. Constructed in the 1950's and operated until 2005, AWE used a pipeline for the authorised discharge of treated effluent. Now redundant, the pipeline is under a care and surveillance regime awaiting decommissioning. The pipeline is some 18.5 km in length and extends from AWE site to the River Thames. Along its route the pipeline passes along and under several major roads, railway lines and rivers as well as travelling through woodland, agricultural land and residential areas. Currently under care and surveillance AWE is considering a number of options for decommissioning the pipeline. One option is to remove the pipeline. In order to assist option evaluation and assess the feasibility of removing the pipeline a decommissioning trial was undertaken and sections of the pipeline were removed within the AWE site. The objectives of the decommissioning trial were to: - Demonstrate to stakeholders that the pipeline can be removed safely, securely and cleanly - Develop a 'tool box' of methods that could be deployed to remove the pipeline - Replicate the conditions and environments encountered along the route of the pipeline The onsite trial was also designed to replicate the physical prevailing conditions and constraints encountered along the remainder of its route i.e. working along a narrow corridor, working in close proximity to roads, working in proximity to above ground and underground services (e.g. Gas, Water, Electricity). By undertaking the decommissioning trial AWE have successfully demonstrated the pipeline can be decommissioned in a safe, secure and clean manor and have developed a tool box of decommissioning techniques. The tool box of includes; - Hot tapping - a method

  8. Time-Action Analysis (TAA) of the Surgical Technique Implanting the Collum Femoris Preserving (CFP) Hip Arthroplasty. TAASTIC trial Identifying pitfalls during the learning curve of surgeons participating in a subsequent randomized controlled trial (An observational study)

    PubMed Central

    van Oldenrijk, Jakob; Schafroth, Matthias U; Bhandari, Mohit; Runne, Wouter C; Poolman, Rudolf W

    2008-01-01

    Background Two types of methods are used to assess learning curves: outcome assessment and process assessment. Outcome measures are usually dichotomous rare events like complication rates and survival or require an extensive follow-up and are therefore often inadequate to monitor individual learning curves. Time-action analysis (TAA) is a tool to objectively determine the level of efficiency of individual steps of a surgical procedure. Methods/Design We are currently using TAA to determine the number of cases needed for surgeons to reach proficiency with a new innovative hip implant prior to initiating a multicentre RCT. By analysing the unedited video recordings of the first 20 procedures of each surgeon the number and duration of the actions needed for a surgeon to achieve his goal and the efficiency of these actions is measured. We constructed a taxonomy or list of actions which together describe the complete surgical procedure. In the taxonomy we categorised the procedure in 5 different Goal Oriented Phases (GOP): 1. the incision phase 2. the femoral phase 3. the acetabulum phase 4. the stem phase 5. the closure pase Each GOP was subdivided in Goal Oriented Actions (GOA) and each GOA is subdivided in Separate Actions (SA) thereby defining all the necessary actions to complete the procedure. We grouped the SAs into GOAs since it would not be feasible to measure each SA. Using the video recordings, the duration of each GOA was recorded as well as the amount of delay. Delay consists of repetitions, waiting and additional actions. The nett GOA time is the total GOA time – delay and is a representation of the level of difficulty of each procedure. Efficiency is the percentage of nett GOA time during each procedure. Discussion This allows the construction of individual learning curves, assessment of the final skill level for each surgeon and comparison of different surgeons prior to participation in an RCT. We believe an objective and comparable assessment of skill

  9. Liquid vs Solid Culture Medium to Evaluate Proportion and Time to Change in Management of Suspects of Tuberculosis—A Pragmatic Randomized Trial in Secondary and Tertiary Health Care Units in Brazil

    PubMed Central

    Moreira, Adriana da Silva Rezende; Huf, Gisele; Vieira, Maria Armanda Monteiro da Silva; da Costa, Paulo Albuquerque; Aguiar, Fábio; Marsico, Anna Grazia; Fonseca, Leila de Souza; Ricks, Mônica; Oliveira, Martha Maria; Detjen, Anne; Fujiwara, Paula Isono; Squire, Stephen Bertel; Kritski, Afranio Lineu

    2015-01-01

    Background The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes. Methods and Findings A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44–.96, p = 0.002, NNT 16, 95% CI 10–39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6–36.4, p = 0.0001). No other important differences were observed. Conclusions This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB. Trial Registration Controlled-Trials.com ISRCTN79888843 PMID:26046532

  10. Is hand hygiene before putting on nonsterile gloves in the intensive care unit a waste of health care worker time?—A randomized controlled trial

    PubMed Central

    Rock, Clare; Harris, Anthony D.; Reich, Nicholas G.; Johnson, J. Kristie; Thom, Kerri A.

    2015-01-01

    Background Hand hygiene (HH) is recognized as a basic effective measure in prevention of nosocomial infections. However, the importance of HH before donning nonsterile gloves is unknown, and few published studies address this issue. Despite the lack of evidence, the World Health Organization and other leading bodies recommend this practice. The aim of this study was to assess the utility of HH before donning nonsterile gloves prior to patient contact. Methods A prospective, randomized, controlled trial of health care workers entering Contact Isolation rooms in intensive care units was performed. Baseline finger and palm prints were made from dominant hands onto agar plates. Health care workers were then randomized to directly don nonsterile gloves or perform HH and then don nonsterile gloves. Postgloving finger and palm prints were then made from the gloved hands. Plates were incubated and colony-forming units (CFU) of bacteria were counted. Results Total bacterial colony counts of gloved hands did not differ between the 2 groups (6.9 vs 8.1 CFU, respectively, P = .52). Staphylococcus aureus was identified from gloves (once in “hand hygiene prior to gloving” group, twice in “direct gloving” group). All other organisms were expected commensal flora. Conclusion HH before donning nonsterile gloves does not decrease already low bacterial counts on gloves. The utility of HH before donning nonsterile gloves may be unnecessary. PMID:23891455

  11. Stroke Trials Registry

    MedlinePlus

    ... Trials News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions ... UT Southwestern Medical Center. Copyright © 1997-2011 - The Internet Stroke Center. All rights reserved. The information contained ...

  12. Trial watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    During the past 20 years, dozens—if not hundreds—of monoclonal antibodies have been developed and characterized for their capacity to mediate antineoplastic effects, either as they activate/enhance tumor-specific immune responses, either as they interrupt cancer cell-intrinsic signal transduction cascades, either as they specifically delivery toxins to malignant cells or as they block the tumor-stroma interaction. Such an intense research effort has lead to the approval by FDA of no less than 14 distinct molecules for use in humans affected by hematological or solid malignancies. In the inaugural issue of OncoImmunology, we briefly described the scientific rationale behind the use of monoclonal antibodies in cancer therapy and discussed recent, ongoing clinical studies investigating the safety and efficacy of this approach in patients. Here, we summarize the latest developments in this exciting area of clinical research, focusing on high impact studies that have been published during the last 15 months and clinical trials launched in the same period to investigate the therapeutic profile of promising, yet hitherto investigational, monoclonal antibodies. PMID:23482847

  13. Trial Watch

    PubMed Central

    Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called ‘out-of-field’ or ‘abscopal’ effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients. PMID:25941606

  14. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology, we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists. PMID:24083080

  15. Trial Watch:

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Cremer, Isabelle; Erbs, Philippe; Limacher, Jean-Marc; Preville, Xavier; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of oncolytic virotherapy in oncological indications. PMID:25097804

  16. Trial Watch

    PubMed Central

    Semeraro, Michaela; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cell-intrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and pro-apoptotic effects on malignant cells, but also interferes with their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications. PMID:24482747

  17. Trial analytics--a tool for clinical trial management.

    PubMed

    Bose, Anindya; Das, Suman

    2012-01-01

    Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.

  18. Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial

    PubMed Central

    Sequeira, Ivana R.; Lentle, Roger G.; Kruger, Marlena C.; Hurst, Roger D.

    2015-01-01

    subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12615000596505 PMID:26629926

  19. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses. Nonetheless, accumulating evidence indicates that a variety of anticancer vaccines, including cell-based, DNA-based, and purified component-based preparations, are capable of circumventing the poorly immunogenic and highly immunosuppressive nature of most tumors and elicit (at least under some circumstances) therapeutically relevant immune responses. Great efforts are currently being devoted to the identification of strategies that may provide anticancer vaccines with the capacity of breaking immunological tolerance and eliciting tumor-associated antigen-specific immunity in a majority of patients. In this sense, promising results have been obtained by combining anticancer vaccines with a relatively varied panels of adjuvants, including multiple immunostimulatory cytokines, Toll-like receptor agonists as well as inhibitors of immune checkpoints. One year ago, in the December issue of OncoImmunology, we discussed the biological mechanisms that underlie the antineoplastic effects of peptide-based vaccines and presented an abundant literature demonstrating the prominent clinical potential of such an approach. Here, we review the latest developments in this exciting area of research, focusing on high-profile studies that have been published during the last 13 mo and clinical trials launched in the same period to evaluate purified peptides or full-length proteins as therapeutic anticancer agents. PMID:24498550

  20. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-12-19

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa.

  1. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-01-01

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa. PMID:25526797

  2. Mock Trials for Children.

    ERIC Educational Resources Information Center

    Hickey, M. Gail

    1990-01-01

    Demonstrates how role-playing in a mock trial situation allows children to view critically both sides of an issue and introduce them to trial procedure. Offers pre-trial activities, ways to teach students to see both sides of a situation, themes for mock trials, and supporting resources. (GG)

  3. Red Light, Purple Light: Findings from a Randomized Trial Using Circle Time Games to Improve Behavioral Self-Regulation in Preschool

    ERIC Educational Resources Information Center

    Tominey, Shauna L.; McClelland, Megan M.

    2011-01-01

    Research Findings: The present study examined the efficacy of a self-regulation intervention with 65 preschool children. Using circle time games, the study examined whether participating in a treatment group significantly improved behavioral self-regulation and early academic outcomes. Half of the children were randomly assigned to participate in…

  4. Effects of an elevated position on time to tracheal intubation by novice intubators using Macintosh laryngoscopy or videolaryngoscopy: randomized crossover trial

    PubMed Central

    Wai, Abraham K. C.; Graham, Colin A.

    2015-01-01

    Objective To investigate the time to tracheal intubation using Glidescope videolaryngoscopy (GVL) compared to that of standard laryngoscopy, by using a Macintosh blade (SLM) in a human patient simulator in supine and elevated (ramped) positions. Methods In this randomized crossover design, novice intubators (first-year medical students), using both laryngoscopic techniques, attempted tracheal intubation on a human patient simulator with a “normal airway” anatomy (Cormack-Lehane grade I). The simulator was placed in both supine and ramped positions using a commercial mattress system. The mean time to intubation and complications were compared between GVL and SLM in both positions. The percentage of glottic opening (POGO, GVL only) was estimated during intubation in the ramped and supine positions. The primary outcome was time to intubation, and the secondary outcomes included complication rates such as esophageal intubation and dental trauma. Results There was no difference in the mean time to intubation in either position (P=0.33). The SLM intubation was significantly faster than GVL (mean difference, 1.5 minutes; P<0.001). The mean POGO score for GVL improved by 8% in the ramped position compared to that in supine position (P=0.018). The esophageal intubation rate for SLM was 15% to 17% compared to 1.3% for GVL; dental trauma occurred in 53% to 56% of GVL, compared to 2% to 6% for SLM (P<0.001, respectively). Conclusion Novices had shorter intubation times using standard laryngoscopy with a SLM compared to GVL in both supine and ramped positions. GVL resulted in fewer esophageal intubations, but more dental trauma than standard laryngoscopy.

  5. A Randomized, controlled, crossover trial to investigate times to onset of the perception of soothing and cooling by over-the-counter heartburn treatments.

    PubMed

    Strugala, V; Dettmar, P W; Sarratt, K; Sykes, J; Berry, P; Thomas, E

    2010-01-01

    This was a randomized, controlled, four-way crossover study in 45 subjects with a tendency to suffer from moderate heartburn following some meals. The study was designed to assess the time to onset of the perceived soothing and cooling effects of the alginate raft-forming products, Gaviscon Liquid (peppermint), Gaviscon Double Action Liquid (peppermint) and Gaviscon Powder Formulation (fresh tropical), compared with a non-active sublingual control. All three Gaviscon products provided significantly faster soothing and cooling effects compared with the control. Based on the upper 95% confidence limits for the median, time to onset of soothing was perceived within 3.15 min, 3.08 min and 4.05 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. Similarly, time to onset of cooling was perceived within 1.95 min, 1.23 min and 11.22 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. The results show that Gaviscon Liquid and Gaviscon Double Action soothe within 3.15 min and cool within 1.95 min. PMID:20515559

  6. Effect of Weight-bearing Therapeutic Exercise on the Q-angle and Muscle Activity Onset Times of Elite Athletes with Patellofemoral Pain Syndrome: A Randomized Controlled Trial

    PubMed Central

    Lee, Jehoon; Lee, Hwangjae; Lee, Wanhee

    2014-01-01

    [Purpose] The purpose of this study was to determine the effect of a weight-bearing therapeutic exercise program for elite athletes diagnosed as having patellofemoral pain syndrome (PFPS). [Subjects] The subjects were 34 elite athletes from the Seoul T Center. They were randomly allocated to three groups: an elastic band exercise group (EBG), a sling exercise group (SEG), or a control group (CG). [Methods] Therapeutic exercises were performed 3 times a week for 8 weeks. The visual analogue scale (VAS) hamstring length, and static and dynamic Q angles were used to test the exercise effect of the exercises, as well as the onset time of electromyographic activity of vastus medialis oblique (VMO) and vastus lateralis (VL). [Results] Decrease of the dynamic Q-angle in EBG was significant and significantly greater than that in CG. The decrease in VAS in SEG was significant and significantly greater than that in CG. There were significant differences in the VL and VMO activity onset times in SEG between pre- and post-test, and their differences between pre- and post-test were also significantly different. [Conclusion] Weight-bearing therapeutic exercise is hoped that clinicians will use this information for better implementation of effective exercise methods for elite athletes with PFPS. PMID:25140080

  7. High-intensity interval training improves VO(2peak), maximal lactate accumulation, time trial and competition performance in 9-11-year-old swimmers.

    PubMed

    Sperlich, Billy; Zinner, Christoph; Heilemann, Ilka; Kjendlie, Per-Ludvik; Holmberg, Hans-Christer; Mester, Joachim

    2010-11-01

    Training volume in swimming is usually very high when compared to the relatively short competition time. High-intensity interval training (HIIT) has been demonstrated to improve performance in a relatively short training period. The main purpose of the present study was to examine the effects of a 5-week HIIT versus high-volume training (HVT) in 9-11-year-old swimmers on competition performance, 100 and 2,000 m time (T(100 m) and T(2,000 m)), VO(2peak) and rate of maximal lactate accumulation (Lac(max)). In a 5-week crossover study, 26 competitive swimmers with a mean (SD) age of 11.5 ± 1.4 years performed a training period of HIIT and HVT. Competition (P < 0.01; effect size = 0.48) and T(2,000 m) (P = 0.04; effect size = 0.21) performance increased following HIIT. No changes were found in T(100 m) (P = 0.20). Lac(max) increased following HIIT (P < 0.01; effect size = 0.43) and decreased after HVT (P < 0.01; effect size = 0.51). VO(2peak) increased following both interventions (P < 0.05; effect sizes = 0.46-0.57). The increases in competition performance, T(2,000 m), Lac(max) and VO(2peak) following HIIT were achieved in significantly less training time (~2 h/week). PMID:20683609

  8. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial.

    PubMed

    Zeymer, Uwe; Montalescot, Gilles; Ardissino, Diego; Bolognese, Leonardo; Clemmensen, Peter; Collet, Jean-Philippe; Lopez-Sendon, Jose; Widimsky, Petr

    2016-06-01

    The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations. PMID:25921481

  9. A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

    PubMed Central

    Yin, Yafu; Mao, Qiufen; Chen, Song; Li, Na; Li, Xuena; Li, Yaming

    2015-01-01

    Abstract This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq 131I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital. Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of 131I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq 131I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of 131I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05. Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319). By a diagnostic scan of 74 MBq 131I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated. PMID:26252311

  10. Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)

    PubMed Central

    Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.

    2012-01-01

    Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365

  11. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials.

    PubMed

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S; Reddy-Luthmoodoo, Medini; Natoli, Alaina K; Owen, Neville; Dunstan, David W; Kingwell, Bronwyn A

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  12. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials

    PubMed Central

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S.; Reddy-Luthmoodoo, Medini; Natoli, Alaina K.; Owen, Neville; Dunstan, David W.; Kingwell, Bronwyn A.

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  13. Clinic-based training in comparison to home-based training after first-time lumbar disc surgery: a randomised controlled trial.

    PubMed

    Johansson, Ann-Christin; Linton, Steven J; Bergkvist, Leif; Nilsson, Olle; Cornefjord, Michael

    2009-03-01

    The effectiveness of physiotherapy after first-time lumbar disc surgery is still largely unknown. Studies in this field are heterogeneous and behavioural treatment principles have only been evaluated in one earlier study. The aim of this randomised study was to compare clinic-based physiotherapy with a behavioural approach to a home-based training programme regarding back disability, activity level, behavioural aspects, pain and global health measures. A total of 59 lumbar disc patients without any previous spine surgery or comorbidity participated in the study. Clinic-based physiotherapy with a behavioural approach was compared to home-based training 3 and 12 months after surgery. Additionally, the home training group was followed up 3 months after surgery by a structured telephone interview evaluating adherence to the exercise programme. Outcome measures were: Oswestry Disability Index (ODI), physical activity level, kinesiophobia, coping, pain, quality of life and patient satisfaction. Treatment compliance was high in both groups. There were no differences between the two groups regarding back pain disability measured by ODI 3 and 12 months after surgery. However, back pain reduction and increase in quality of life were significantly higher in the home-based training group. The patients in the clinic-based training group had significantly higher activity levels 12 months after surgery and were significantly more satisfied with physiotherapy care 3 months after surgery compared to the home-based training group. Rehabilitation after first-time lumbar disc surgery can be based on home training as long as the patients receive both careful instructions from a physiotherapist and strategies for active pain coping, and have access to the physiotherapist if questions regarding training arise. This might be a convenient treatment arrangement for most patients. PMID:19020904

  14. Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

    NASA Astrophysics Data System (ADS)

    Bugaj, Joseph E.; Dorshow, Richard B.

    2014-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

  15. A Comparative Randomized Trial on the Optimal Timing of Dexamethasone for Pain Relief after Endoscopic Submucosal Dissection for Early Gastric Neoplasm

    PubMed Central

    Pyo, Jeung Hui; Lee, Hyuk; Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Jae J.

    2016-01-01

    Background/Aims The aim of this study was to compare the clinical effects of preoperative and postoperative dexamethasone on pain after endoscopic submucosal dissection (ESD) for early gastric neoplasm. Methods Forty patients with early gastric neoplasm who were scheduled for ESD were randomized into two groups according to the timing of steroid administration: preoperative (“pre”, n=20) and postoperative (“post”, n=20) steroid administration. The pre group received 0.15 mg/kg dexamethasone before ESD and placebo after, and the post group received pre-ESD placebo and post-ESD dexamethasone. The present pain intensity (PPI) index and the short-form McGill pain (SF-MP) questionnaire were evaluated. Results The primary outcome was PPI score at 6 hours after ESD. There was a greater reduction in 6-hour PPI in the pre group than in the post group (2.1±0.8 vs 3.0±1.1, respectively; p=0.006). The immediate PPI was also significantly lower in the pre group than in the post group (1.6±0.6 vs 2.9±0.6, respectively; p<0.001), and the total SF-MP scores were significantly lower in the pre group than in the post group both immediately and at 6 hours after the operation. Conclusions Preoperative administration of dexamethasone may produce a superior analgesic effect in patients who undergo ESD compared with the postoperative administration of dexamethasone. PMID:27114413

  16. Prevalence and risk factors for low bone mineral density in untreated HIV infection: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Carr, Andrew; Grund, Birgit; Neuhaus, Jacqueline; Schwartz, Ann; Bernardino, Jose I; White, David; Badel-Faesen, Sharlaa; Avihingsanon, Anchalee; Ensrud, Kristine; Hoy, Jennifer

    2014-01-01

    Background HIV infection is associated with a higher prevalence of low bone mineral density (BMD) and fractures than the general population. There are limited data in HIV-positive adults, naïve to antiretroviral therapy (ART), to estimate the relative contribution of untreated HIV to bone loss. Methods The START Bone Mineral Density substudy is a randomised comparison of the effect of immediate versus deferred initial ART on bone. We evaluated traditional, demographic, HIV-related, and immunological factors for their associations with baseline hip and lumbar spine BMD, measured by dual-energy x-ray absorptiometry, using multiple regression. Results A total of 424 ART-naïve participants were enrolled at 33 sites in six continents; mean (SD) age was 34 (10.1) years, 79.0% were nonwhite, 26.0% were women, and 12.5% had a body mass index (BMI) <20 kg/m2. Mean (SD) Z-scores were -0.41 (0.94) at the spine and -0.36 (0.88) for total hip; 1.9% had osteoporosis and 35.1% had low BMD (hip or spine T-score <-1.0). Factors independently associated with lower BMD at the hip and spine were female sex, Latino/Hispanic ethnicity, lower BMI and higher estimated glomerular filtration rate. Longer time since HIV diagnosis was associated with lower hip BMD. Current or nadir CD4 cell counts, and HIV viral load were not associated with BMD. Conclusions In this geographically and racially diverse population of ART-naïve adults with normal CD4 cell counts, low BMD was common, but osteoporosis was rare. Lower BMD was significantly associated with traditional risk factors but not with CD4 cell count or viral load. PMID:25711332

  17. The Quality of Registration of Clinical Trials

    PubMed Central

    Viergever, Roderik F.; Ghersi, Davina

    2011-01-01

    Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

  18. Male contraceptives under trial.

    PubMed

    1975-02-01

    The International Planned Parenthood Federation held its 4th biological workshop in New Delhi on October 17-19, 1974. The topic of this meeting was "Agents affecting fertility in the male." 10 internationally known experts in the field of male reproductive physiology attended and each presented an up-to-the-minute account of their work in the field, followed by a full discussion. Much basic work was described, and the results of the latest human trials of male contraceptives were reported. Dr. F. Neumann of the Schering Company, Berlin, reported on clinical trials of the drug cyproterone acetate. This drug has been in the news for some time as a possible male contraceptive. It is found that small doses prevent sperm from maturing in the epididymis. This drug is already on the British market as Androcur. In large doses it is useful for curbing libido, and in this format it is used to control "sexual offenders." In the small doses at which it is useful as a contraceptive, the effects on libido are negligible, and the drug is at present undergoing human trials as a contraceptive agent. However, much work has still be done on, for example, long-term side effects. Another approach described by Dr. J. Frick from Innsbruck, Austria, is that of giving men a progestagen combined with testosterone. Whereas the progestagen has the effect of inhibiting sperm production in the testis, the testosterone compensates for androgen loss and maintains libido and male characteristics. Dr. Frick reported studies using 15 progestagen combinations, including a new drug provisionally titled R2323. The overall conclusion of the meeting was that there are still many problems to be solved, and it will be some years before a male contraceptive will be commercially available. PMID:12333962

  19. Effect of Educational Outreach Timing and Duration on Facility Performance for Infectious Disease Care in Uganda: A Trial with Pre-Post and Cluster Randomized Controlled Components

    PubMed Central

    Burnett, Sarah M.; Mbonye, Martin K.; Naikoba, Sarah; Zawedde-Muyanja, Stella; Kinoti, Stephen N.; Ronald, Allan; Rubashembusya, Timothy; Willis, Kelly S.; Colebunders, Robert; Manabe, Yukari C.; Weaver, Marcia R.

    2015-01-01

    Background Classroom-based learning is often insufficient to ensure high quality care and application of health care guidelines. Educational outreach is garnering attention as a supplemental method to enhance health care worker capacity, yet there is little information about the timing and duration required to improve facility performance. We sought to evaluate the effects of an infectious disease training program followed by either immediate or delayed on-site support (OSS), an educational outreach approach, on nine facility performance indicators for emergency triage, assessment, and treatment; malaria; and pneumonia. We also compared the effects of nine monthly OSS visits to extended OSS, with three additional visits over six months. Methods This study was conducted at 36 health facilities in Uganda, covering 1,275,960 outpatient visits over 23 months. From April 2010 to December 2010, 36 sites received infectious disease training; 18 randomly selected sites in arm A received nine monthly OSS visits (immediate OSS) and 18 sites in arm B did not. From March 2011 to September 2011, arm A sites received three additional visits every two months (extended OSS), while the arm B sites received eight monthly OSS visits (delayed OSS). We compared the combined effect of training and delayed OSS to training followed by immediate OSS to determine the effect of delaying OSS implementation by nine months. We also compared facility performance in arm A during the extended OSS to immediate OSS to examine the effect of additional, less frequent OSS. Results Delayed OSS, when combined with training, was associated with significant pre/post improvements in four indicators: outpatients triaged (44% vs. 87%, aRR = 1.54, 99% CI = 1.11, 2.15); emergency and priority patients admitted, detained, or referred (16% vs. 31%, aRR = 1.74, 99% CI = 1.10, 2.75); patients with a negative malaria test result prescribed an antimalarial (53% vs. 34%, aRR = 0.67, 99% CI = 0.55, 0.82); and pneumonia

  20. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  1. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  2. Teaching Drama Via Trials.

    ERIC Educational Resources Information Center

    Mansour, Wisam

    1998-01-01

    Suggests using a court trial as an activity for teaching drama to English-as-a-foreign-language (EFL) students. Describes use of a court trial for teaching Macbeth to EFL students in Jordan. (Author/VWL)

  3. DIFFERENCES IN GROUND CONTACT TIME EXPLAIN THE LESS EFFICIENT RUNNING ECONOMY IN NORTH AFRICAN RUNNERS

    PubMed Central

    Granados, C.; Irazusta, J.; Bidaurrazaga-Letona, I.; Zabala-Lili, J.; Tam, N.; Gil, S.M.

    2013-01-01

    The purpose of this study was to investigate the relationship between biomechanical variables and running economy in North African and European runners. Eight North African and 13 European male runners of the same athletic level ran 4-minute stages on a treadmill at varying set velocities. During the test, biomechanical variables such as ground contact time, swing time, stride length, stride frequency, stride angle and the different sub-phases of ground contact were recorded using an optical measurement system. Additionally, oxygen uptake was measured to calculate running economy. The European runners were more economical than the North African runners at 19.5 km · h−1, presented lower ground contact time at 18 km · h−1 and 19.5 km · h−1 and experienced later propulsion sub-phase at 10.5 km · h−1,12 km · h−1, 15 km · h−1, 16.5 km · h−1 and 19.5 km · h−1 than the European runners (P < 0.05). Running economy at 19.5 km · h−1 was negatively correlated with swing time (r = -0.53) and stride angle (r = -0.52), whereas it was positively correlated with ground contact time (r = 0.53). Within the constraints of extrapolating these findings, the less efficient running economy in North African runners may imply that their outstanding performance at international athletic events appears not to be linked to running efficiency. Further, the differences in metabolic demand seem to be associated with differing biomechanical characteristics during ground contact, including longer contact times. PMID:24744486

  4. Does an L-glutamine-containing, Glucose-free, Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

    PubMed Central

    Gutiérrez, Claudia; Villa, Sofía; Mota, Felipe R.; Calva, Juan J.

    2007-01-01

    This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1–60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea. PMID:18330060

  5. Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial

    PubMed Central

    Mehran, Roxana; Pocock, Stuart J.; Stone, Gregg W.; Clayton, Tim C.; Dangas, George D.; Feit, Frederick; Manoukian, Steven V.; Nikolsky, Eugenia; Lansky, Alexandra J.; Kirtane, Ajay; White, Harvey D.; Colombo, Antonio; Ware, James H.; Moses, Jeffrey W.; Ohman, E. Magnus

    2009-01-01

    Aims To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied. Methods and Results A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year. Conclusion After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk. PMID:19351691

  6. Salem Witch Trials.

    ERIC Educational Resources Information Center

    Ray, Benjamin

    2003-01-01

    Presents a lesson plan that focuses on the Salem (Massachusetts) witchcraft trials. Explains that the first section of the lesson has students learn about the trials as described in the court records. The second section asks students to interpret various images of the trials. (CMK)

  7. Desulfotomaculum spp.and Methanobacterium spp. Dominate a 4-5 km Deep Fault

    SciTech Connect

    Moser, Duane P.; Gihring, Thomas M.; Brockman, Fred J.; Fredrickson, Jim K.; Balkwill, David L.; Dollhopf, M E.; Lollar, B S.; Pratt, Lisa; Boice, E.; Southam, G; Wanger, Greg; Baker, Brett; Pfiffner, S; Lin, L; Onstott, T C.

    2005-12-01

    Sulfidic, 54-60 C, 3 to 30 million year old meteoric water stably Alkaline, sulfidic, 54 to 60 C, 4 to 53 million-year-old meteoric water emanating from a borehole intersecting quartzite-hosted fractures >3.3 km beneath the surface supported a microbial community dominated by a bacterial species affiliated with Desulfotomaculum spp. and an archaeal species related to Methanobacterium spp. The geochemical homogeneity over the 650-m length of the borehole, the lack of dividing cells, and the absence of these microorganisms in mine service water support an indigenous origin for the microbial community. The coexistence of these two microorganisms is consistent with a limiting flux of inorganic carbon and SO4 2 in the presence of high pH, high concentrations of H2 and CH4, and minimal free energy for autotrophic methanogenesis. Sulfide isotopic compositions were highly enriched, consistent with microbial SO4 2 reduction under hydrologic isolation. An analogous microbial couple and similar abiogenic gas chemistry have been reported recently for hydrothermal carbonate vents of the Lost City near the Mid-Atlantic Ridge (D. S. Kelly et al., Science 307:1428-1434, 2005), suggesting that these features may be common to deep subsurface habitats (continental and marine) bearing this geochemical signature. The geochemical setting and microbial communities described here are notably different from microbial ecosystems reported for shallower continental subsurface environments.

  8. Paperless clinical trials: Myth or reality?

    PubMed Central

    Gupta, Sandeep K.

    2015-01-01

    There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

  9. Use of a Structured Mirrors Intervention Does Not Reduce Delirium Incidence But May Improve Factual Memory Encoding in Cardiac Surgical ICU Patients Aged Over 70 Years: A Pilot Time-Cluster Randomized Controlled Trial

    PubMed Central

    Giraud, Kimberly; Pontin, Megan; Sharples, Linda D.; Fletcher, Paul; Dalgleish, Tim; Eden, Allaina; Jenkins, David P.; Vuylsteke, Alain

    2016-01-01

    Introduction: Post-operative delirium remains a significant problem, particularly in the older surgical patient. Previous evidence suggests that the provision of supplementary visual feedback about ones environment via the use of a mirror may positively impact on mental status and attention (core delirium diagnostic domains). We aimed to explore whether use of an evidence-based mirrors intervention could be effective in reducing delirium and improving post-operative outcomes such as factual memory encoding of the Intensive Care Unit (ICU) environment in older cardiac surgical patients. Methods: This was a pilot time-cluster randomized controlled trial at a 32-bed ICU, enrolling 223 patients aged 70 years and over, admitted to ICU after elective or urgent cardiac surgery from October 29, 2012 to June 23, 2013. The Mirrors Group received a structured mirrors intervention at set times (e.g., following change in mental status). The Usual Care Group received the standard care without mirrors. Primary outcome was ICU delirium incidence; secondary outcomes were ICU delirium days, ICU days with altered mental status or inattention, total length of ICU stay, physical mobilization (balance confidence) at ICU discharge, recall of factual and delusional ICU memories at 12 weeks, Health-Related Quality of Life at 12 weeks, and acceptability of the intervention. Results: The intervention was not associated with a significant reduction in ICU delirium incidence [Mirrors: 20/115 (17%); Usual Care: 17/108 (16%)] or duration [Mirrors: 1 (1–3); Usual Care: 2 (1–8)]. Use of the intervention on ICU was predictive of significantly higher recall of factual (but not delusional) items at 12 weeks after surgery (p = 0.003) and acceptability was high, with clinicians using mirrors at 86% of all recorded hourly observations. The intervention did not significantly impact on other secondary outcomes. Conclusion: Use of a structured mirrors intervention on the post-operative ICU does not

  10. Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice

    PubMed Central

    Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

    2016-01-01

    Objectives 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. Design Cohort study of trials with systematic searches for published results. Setting Clinical drug trials in Norwegian general practice. Methods 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. Main outcome measures We determined the frequency of publication of trial results and trial characteristics associated with publication of results. 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 (χ2 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. Conclusions 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. PMID:27067893

  11. How experimental trial context affects perceptual categorization

    PubMed Central

    Palmeri, Thomas J.; Mack, Michael L.

    2015-01-01

    To understand object categorization, participants are tested in experiments often quite different from how people experience object categories in the real world. Learning and knowledge of categories is measured in discrete experimental trials, those trials may or may not provide feedback, trials appear one after another, after some fixed inter-trial interval, with hundreds of trials in a row, within experimental blocks with some structure dictated by the experimental design. In the real world, outside of certain educational and vocational contexts, opportunities to learn and use categories are intermixed over time with a whole multitude of intervening experiences. It is clear from any elementary understanding of human cognition that sequential effects matter, yet this understanding is often ignored, and categorization trials are often instead treated as independent events, immune to local trial context. In this perspective, we use some of our work to illustrate some of the consequences of the fact that categorization experiments have a particular trial structure. Experimental trial context can affect performance in category learning and categorization experiments in ways that can profoundly affect theoretical conclusions. PMID:25745412

  12. Time course of soil carbon storage, 15N and radiocarbon signature in top- and subsoil of a 60-years agricultural field trial - indications for compensating effects of carbon input and turnover

    NASA Astrophysics Data System (ADS)

    Leifeld, Jens; Conen, Franz; Oberholzer, Hans Rudolf; Jochen, Mayer

    2014-05-01

    Soil carbon dynamics are controlled by the delicate balance between carbon inputs and outputs which both are co-regulated by land use and management (LUM) as important anthropogenic drivers. Upon land use change to cropland carbon stocks generally tend to decline but often the contribution of two opposing factors, namely changes in input and decomposition rates, to soil carbon stock changes is indistinguishable. Here we report on an ongoing cropland experiment in Zurich, Switzerland, named ZOFE (Zurich Organic Fertilization Experiment), established on former grassland in 1949. ZOFE encompasses a range of mineral and organic fertilization practices and a zero fertilizer treatment as control. The experiment has a block design with five replicates per treatment. We make use of productivity and fertilization gradients in selected treatments of the ZOFE trial to evaluate how low or high inputs (induced by differential yields and organic fertilization) may affect soil organic carbon storage and transformation. For the most recent sampling that also included subsoil down to 0.9 m, all properties were measured for every single replicate. Topsoil carbon storage declined after grassland conversion at rates of c. 0.2 t C ha-1 a-1, particularly in treatments with mineral fertilizer and high yields, and without fertilization and low yields. Organic matter amendments such as manure or compost could partially offset but not fully compensate some of the topsoil carbon loss. Over time the soil's delta 15N signature declined as well, probably due to increased atmospheric nitrogen deposition. It increased from the top- to the subsoil, indicating increasing microbial transformation, particularly with manure added. The soil's radiocarbon signature revealed distinct bomb peak patterns in all treatments but only in the topsoil. The 14C data confirmed that with higher productivity more recent organic matter was incorporated, both in top and subsoil. Because, in contrast to topsoil

  13. Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts >500 cells/μL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    KUNISAKI, Ken M.; NIEWOEHNER, Dennis E.; COLLINS, Gary; NIXON, Daniel E.; TEDALDI, Ellen; AKOLO, Christopher; KITYO, Cissy; KLINKER, Hartwig; LA ROSA, Alberto; CONNETT, John E.

    2014-01-01

    Objectives To describe the prevalence and correlates of chronic obstructive pulmonary disease (COPD) in a multicentre international cohort of persons living with HIV (PLWH). Methods We performed a cross-sectional analysis of adult PLWH, naïve to HIV treatment, with baseline CD4 cell count >500 cells/μL enrolled in the Pulmonary Substudy of the Strategic Timing of AntiRetroviral Treatment trial. We collected standardised, quality-controlled spirometry. COPD was defined as forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio less than the lower limit of normal. Results Among 1026 participants from 80 sites and 20 countries, median (IQR) age was 36 (30, 44) years, 29% were female, and time since HIV diagnosis was 1.2 (0.4, 3.5) years. Baseline CD4 cell count was 648 (583, 767) cells/μL, viral load was 4.2 (3.5, 4.7) log10 copies/mL, and 10% had viral load ≤400 copies/mL despite lack of HIV treatment. Current/former/never smokers comprised 28%/11%/61% of the cohort, respectively. COPD was present in 6.8% of participants, and varied by age, smoking status, and region. 48% of those with COPD reported lifelong nonsmoking. In multivariable regression, age and pack-years of smoking had the strongest associations with FEV1/FVC ratio (p<0.0001). There were significant differences between the effect of region on FEV1/FVC ratio (p=0.010). Conclusions Our data suggest that among PLWH, naïve to HIV treatment and with CD4 cell count >500 cells/μL, smoking and age are important factors related to COPD. Smoking cessation should remain a high global priority for clinical care and research in PLWH. PMID:25711330

  14. From international to zonal trials: the origins of the Nuremberg medical trial.

    PubMed

    Weindling, P

    2000-01-01

    This article examines how plans to have a second International Military Tribunal led to the Medical Trial at Nuremberg. While the British opposed a second international trial because of their distrust of the Soviets, they supported a plan for a series of special zonal trials to be conducted by the American authorities at Nuremberg. In December 1945 the British became aware of the extent of medical war crimes committed by the Germans. Their investigation led to an eventual handover to the Americans of a group of German doctors for trial at Nuremberg. At the same time the British and French Supported an International Scientific Commission for the Investigation of Medical War Crimes.

  15. [Phase I cancer trials methodology].

    PubMed

    Le Tourneau, Christophe; Faivre, Sandrine; Raymond, Eric; Diéras, Véronique

    2007-11-01

    The main objective of phase I cancer trials is to determine precisely the recommended dose of an anticancer agent as a single agent or in a context of combinations of anticancer agents (including cytotoxic agents, immunotherapy, radiotherapy...), that is administered for the first time in man, to further proceed clinical development with phase II and III trials. The recommended dose must have the greatest efficiency with acceptable toxicity. For the anticancer agents, the ratio risk/benefit is high, since toxicities associated with many cancer therapeutic agents are substantial and because the efficacy is often limited. Thus, phase I cancer trials present unique challenges in comparison to other therapeutic areas. Indeed, it is essential to minimize the numbers of patients treated at subefficient dose levels, and in the same time not to expose the patients to unacceptable toxicity. Historically, the first method that has been used is the Fibonacci escalation. The major problems raised with this method have been the lengths of the trials and the risk to treat substantial numbers of patients at nontherapeutix doses. Thus, novel methods have been then developed modifying the numbers of patients included at each dose level and the rapidity of dose escalation. These methods include pharmacologically guided dose escalation, escalation with overdose control and the continual reassessment method which are both statistically based dose escalation methods, and the accelerated titration designs. Concerning the targeted anticancer therapies, the therapeutic effect on the target, due to their higher specificity, can be obtained using doses that have few toxicity. Using the toxicity to determine the recommended dose for phase II trials, as it is the case for "classical > anticancer agents, does not seem to be sufficient. Alternatives to determine the optimal biological dose include measurement of target inhibition, pharmacokinetic analysis and functional imaging.

  16. More outcomes than trials: a call for consistent data collection across stroke rehabilitation trials.

    PubMed

    Ali, M; English, C; Bernhardt, J; Sunnerhagen, K S; Brady, M

    2013-01-01

    Stroke survivors experience complex combinations of impairments, activity limitations, and participation restrictions. The essential components of stroke rehabilitation remain elusive. Determining efficacy in randomized controlled trials (RCTs) is challenging; there is no commonly agreed primary outcome measure for rehabilitation trials. Clinical guidelines depend on proof of efficacy in RCTs and meta-analyses. However, diverse trial aims, differing methods, inconsistent data collection, and use of multiple assessment tools hinder comparability across trials. Consistent data collection in acute stroke trials has facilitated meta-analyses to inform trial design and clinical practice. With few exceptions, inconsistent data collection has hindered similar progress in stroke rehabilitation research. There is an urgent need for the routine collection of a core dataset of common variables in rehabilitation trials. The European Stroke Organisation Outcomes Working Group, the National Institutes of Neurological Disorders and Stroke Common Data Elements project, and the Collaborative Stroke Audit and Research project have called for consistency in data collection in stroke trials. Standardizing data collection can decrease study start up times, facilitate data sharing, and inform clinical guidelines. Although achieving consensus on which outcome measures to use in stroke rehabilitation trials is a considerable task, perhaps a feasible starting point is to achieve consistency in the collection of data on demography, stroke severity, and stroke onset to inclusion times. Longer term goals could include the development of a consensus process to establish the core dataset. This should be endorsed by researchers, funders, and journal editors in order to facilitate sustainable change.

  17. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports.

  18. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports. PMID:20674592

  19. The clinical trial.

    PubMed

    Chalmers, T C

    1981-01-01

    This paper argues that scientific clinical trials are the most ethical way to benefit patients whenever there is uncertainty about proper diagnosis and therapy. An increasing number of trials reported in clinical journals have employed randomization since the 1st extensive use of randomized controlled trials after the 2nd World War. A review of 4 examples of the response of physicians to trial results that differ from their own opinions indicates considerable reluctance to accept the results, no matter how well the trials were designed. Such reluctance may gradually disappear as physicians become better educated in clinical trial methodology. A good trial requires that unconscious bias be controlled, that data be recorded in detail and expertly analyzed, and that the sample size be considered when interpreting the results. Procedures designed to handle the ethical issues related to clinical trials include peer review, informed consent, initiation of randomization with the 1st use of a new therapy, reference to the previous outcomes in protocols and informed consent procedures and deferring decisions about when to stop studies to 3rd parties (such as data monitoring committees or policy advisory boards) and avoiding the use of placebos when an effective therapy is known. It is recommended that money for clinical trials be provided from the general medical care budget rather than the 2% that is devoted to all biomedical research.

  20. COMPETING COMMITMENTS in CLINICAL TRIALS

    PubMed Central

    Lidz, Charles W.; Appelbaum, Paul S.; Joffe, Steven; Albert, Karen; Rosenbaum, Jill; Simon, Lorna

    2013-01-01

    Most discussion about clinical care in clinical trials has concerned whether subjects’ care may be compromised by research procedures. The possibility that clinical researchers might give priority to helping their “patients” even if that required deviating from the imperatives of the research protocol largely has been ignored. We conducted an on-line survey with clinical researchers, including physicians, research nurses and other research staff, to assess the ways and frequency with which clinical trials may be at risk for being compromised by clinical researchers’ attempting to address the clinical needs of subjects. The survey covered recruitment, clinical management while in the trial, and termination decisions. It produced a 72.0% response rate. Over 20% of respondents agreed that researchers should deviate from the protocol to improve subjects’ care; 28% reported that medications restricted by the protocol were given; 21% reported that subjects who were not eligible had been recruited; and 9% said subjects had been retained in a trial despite meeting termination criteria. Some respondents reported that these deviations from the protocol happened many times. The ramifications of these findings are discussed. PMID:19873835

  1. Characteristics of drug combination therapy in oncology by analyzing clinical trial data on ClinicalTrials.gov.

    PubMed

    Wu, Menghua; Sirota, Marina; Butte, Atul J; Chen, Bin

    2015-01-01

    Within the past few decades, drug combination therapy has been intensively studied in oncology and other complex disease areas, especially during the early drug discovery stage, as drug combinations have the potential to improve treatment response, minimize development of resistance or minimize adverse events. In the present, designing combination trials relies mainly on clinical and empirical experience. While empirical experience has indeed crafted efficacious combination therapy clinical trials (combination trials), however, garnering experience with patients can take a lifetime. The preliminary step to eliminating this barrier of time, then, is to understand the current state of combination trials. Thus, we present the first large-scale study of clinical trials (2008-2013) from ClinicalTrials.gov to compare combination trials to non-combination trials, with a focus on oncology. In this work, we developed a classifier to identify combination trials and oncology trials through natural language processing techniques. After clustering trials, we categorized them based on selected characteristics and observed trends present. Among the characteristics studied were primary purpose, funding source, endpoint measurement, allocation, and trial phase. We observe a higher prevalence of combination therapy in oncology (25.6% use combination trials) in comparison to other disease trials (6.9%). However, surprisingly the prevalence of combinations does not increase over the years. In addition, the trials supported by the NIH are significantly more likely to use combinations of drugs than those supported by industry. Our preliminary study of current combination trials may facilitate future trial design and move more preclinical combination studies to the clinical trial stage.

  2. Duration of First Off-Treatment Interval Is Prognostic for Time to Castration Resistance and Death in Men With Biochemical Relapse of Prostate Cancer Treated on a Prospective Trial of Intermittent Androgen Deprivation

    PubMed Central

    Yu, Evan Y.; Gulati, Roman; Telesca, Donatello; Jiang, Peter; Tam, Stephen; Russell, Kenneth J.; Nelson, Peter S.; Etzioni, Ruth D.; Higano, Celestia S.

    2010-01-01

    Purpose This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis. PMID:20421544

  3. Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

    PubMed Central

    Wiljer, David; Cafazzo, Joseph A

    2016-01-01

    Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study

  4. Clinical trials in children

    PubMed Central

    Joseph, Pathma D; Craig, Jonathan C; Caldwell, Patrina HY

    2015-01-01

    Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children. PMID:24325152

  5. Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: a substudy from the BENEFIT trial.

    PubMed

    Moreira, Otacilio C; Ramírez, Juan David; Velázquez, Elsa; Melo, Myllena F A Dias; Lima-Ferreira, Carolina; Guhl, Felipe; Sosa-Estani, Sergio; Marin-Neto, Jose Antonio; Morillo, Carlos A; Britto, Constança

    2013-01-01

    Quantitative real-time PCR (qPCR) is an accurate method to quantify Trypanosoma cruzi DNA and can be used to follow-up parasitemia in Chagas disease (CD) patients undergoing chemotherapy. The Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) study is an international, multicenter, randomized, double-blinded and placebo-controlled clinical trial to evaluate the efficacy of benznidazole (BZ) treatment in patients with chronic Chagas cardiomyopathy (CCC). One important question to be addressed concerns the effectiveness of BZ in reducing overall parasite load in CCC patients, even in the absence of parasitological cure. This report describes the evaluation of multiple procedures for DNA extraction and qPCR-based protocols aiming to establish a standardized methodology for the absolute quantification of T. cruzi DNA in Guanidine-EDTA blood (GEB) samples. A panel of five primer sets directed to the T. cruzi nuclear satellite DNA repeats (Sat-DNA) and to the minicircle DNA conserved regions (kDNA) was compared in either SYBR Green or TaqMan systems. Standard curve parameters such as, amplification efficiency, coefficient of determination and intercept were evaluated, as well as different procedures to generate standard samples containing pre-established T. cruzi DNA concentration. Initially, each primer set was assayed in a SYBR Green qPCR to estimate parasite load in GEB samples from chronic Chagas disease patients. The results achieved from Bayesian transmutability analysis elected the primer sets Cruzi1/Cruzi2 (p=0.0031) and Diaz7/Diaz8 (p=0.0023) coupled to the QIAamp DNA Kit extraction protocol (silica gel column), as the most suitable for monitoring parasitemia in these patients. Comparison between the parasite burden of 150 GEB samples of BENEFIT patients from Argentina, Brazil and Colombia, prior to drug/placebo administration, was performed using Cruzi1/Cruzi2 primers in a SYBR Green approach. The median parasitemia found in patients from

  6. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672

  7. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)

  8. Improving the operational efficiency of Phase 2 and 3 trials.

    PubMed

    Ganju, Jitendra

    2016-01-01

    The period toward the end of patients' participation in late stage blinded clinical trials is highly resource intensive for the sponsor. Consider first a Phase 3 trial. If the trial is a success, the sponsor has to implement the next steps, which might be filing for approval of the drug with the US Food and Drug Administration (FDA). To shorten the time interval between trial completion and submission of the package to the FDA, sponsors front-load as much work as is possible at risk. The approach is efficient if the trial succeeds but is inefficient if it fails. For a failed trial, the sponsor is unlikely to proceed with the plan that assumed success. Phase 2 trials are also at risk of being inefficient. Many activities, such as planning for drug interaction studies, thorough QT studies, or site selection for Phase 3 trials, are set in motion prior to completion of the Phase 2 trial. The work going on in parallel is wasted if the trial fails. The proposal to improve the efficiency is to let an independent entity provide the sponsor critical information at an earlier time necessary to reevaluate activities ongoing in parallel and external to the trial. PMID:27439520

  9. Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery.

    PubMed

    Fan, Jui-Lin; Bourdillon, Nicolas; Kayser, Bengt

    2013-08-01

    During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia.

  10. Practical Issues when Planning for Field Trials

    NASA Astrophysics Data System (ADS)

    Andersson, Susanne; Andersson, Anna-Lena

    This chapter is written from a test site leader perspective and describes the role of planning and timing of field trials when testing technical solutions, which could enable people with dementia to live a more independent life. The chapter is based on experiences from setting up the first and second field trials in the three test sites of the COGKNOW project. The intention is to point out some key issues that are important in preparation and planning of a field trial. The chapter addresses issues in the preparatory, the actual and the post-test phase of the field trial in order to help achieve a high level of success both from a general perspective and with a special focus on people with dementia.

  11. Clinical Trials - Participants

    MedlinePlus

    ... participating in was reviewed by an IRB. Further Reading For more information about research protections, see: Office ... data and decide whether the results have medical importance. Results from clinical trials are often published in ...

  12. Polyp Prevention Trial

    Cancer.gov

    The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat, high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous polyps of the large bowel.

  13. Anchor Trial Launch

    Cancer.gov

    NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

  14. Apps for IMproving FITness and Increasing Physical Activity Among Young People: The AIMFIT Pragmatic Randomized Controlled Trial

    PubMed Central

    Jiang, Yannan; Whittaker, Robyn; Maddison, Ralph

    2015-01-01

    Background Given the global prevalence of insufficient physical activity (PA), effective interventions that attenuate age-related decline in PA levels are needed. Mobile phone interventions that positively affect health (mHealth) show promise; however, their impact on PA levels and fitness in young people is unclear and little is known about what makes a good mHealth app. Objective The aim was to determine the effects of two commercially available smartphone apps (Zombies, Run and Get Running) on cardiorespiratory fitness and PA levels in insufficiently active healthy young people. A second aim was to identify the features of the app design that may contribute to improved fitness and PA levels. Methods Apps for IMproving FITness (AIMFIT) was a 3-arm, parallel, randomized controlled trial conducted in Auckland, New Zealand. Participants were recruited through advertisements in electronic mailing lists, local newspapers, flyers posted in community locations, and presentations at schools. Eligible young people aged 14-17 years were allocated at random to 1 of 3 conditions: (1) use of an immersive app (Zombies, Run), (2) use of a nonimmersive app (Get Running), or (3) usual behavior (control). Both smartphone apps consisted of a fully automated 8-week training program designed to improve fitness and ability to run 5 km; however, the immersive app featured a game-themed design and narrative. Intention-to-treat analysis was performed using data collected face-to-face at baseline and 8 weeks, and all regression models were adjusted for baseline outcome value and gender. The primary outcome was cardiorespiratory fitness, objectively assessed as time to complete the 1-mile run/walk test at 8 weeks. Secondary outcomes were PA levels (accelerometry and self-reported), enjoyment, psychological need satisfaction, self-efficacy, and acceptability and usability of the apps. Results A total of 51 participants were randomized to the immersive app intervention (n=17), nonimmersive

  15. Strategies to improve retention in randomised trials

    PubMed Central

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-01-01

    severe symptoms do not return questionnaires or attend a follow-up visit, this will bias the findings of the trial. Many methods are used by researchers to keep people in trials. These encourage people to send back data by questionnaire, return to a clinic or hospital for trial-related tests, or be seen by a health or community care worker. Study characteristics This review identified methods that encouraged people to stay in trials. We searched scientific databases for randomised studies (where people are allocated to one of two or more possible treatments in a random manner) or quasi-randomised studies (where allocation is not really random, e.g. based on date of birth, order in which they attended clinic) that compared methods of increasing retention in trials. We included trials of participants from any age, gender, ethnic, cultural, language and geographic groups. Key results The methods that appeared to work were offering or giving a small amount of money for return of a completed questionnaire and enclosing a small amount of money with a questionnaire with the promise of a further small amount of money for return of a filled in questionnaire. The effect of other ways to keep people in trials is still not clear and more research is needed to see if these really do work. Such methods are shorter questionnaires, sending questionnaires by recorded delivery, using a trial design where people know which treatment they will receive, sending specially designed letters with a reply self addressed stamped envelope followed by a number of reminders, offering a donation to charity or entry into a prize draw, sending a reminder to the study site about participants to follow-up, sending questionnaires close to the time the patient was last followed-up, managing peoples' follow-up, conducting follow-up by telephone and changing the order of questionnaire questions. Quality of evidence The methods that we identified were tested in trials run in many different disease areas and

  16. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

    PubMed Central

    2012-01-01

    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