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At least 163 records · Page 9Linked to original sources

PubMed1998

Interpretation of accelerants in blood of cadavers found in the wreckage after fire.

Accelerants in the blood of 73 cadavers found in wreckage after fire were analyzed by gas chromatography (GC) and a combination of gas chromatography-mass spectrometry (GC-MS) to decide whether accelerants containing petroleum components had been used and whether the cadavers had been exposed to fire before or after death. In 16 of 26 cases in which accelerants were used to start a fire before death, accelerants were detected in the blood. In 7 cases in which accelerants were used to start a fire, the victims were determined to have been exposed to the vapor of accelerants after death because no accelerants were detected in the blood, no soot was found in the airways, and carboxyhemoglobin (COHb) concentrations were not higher than those found in smokers. In 9 of 34 cases in which accelerants were suspected to have been used to start a fire before death, accelerants were detected in the blood. When soot is not detectable by the unaided eye in the airways of a victim found in debris of a fire in which the use of accelerants is suspected, or the COHb concentration in the blood is no higher than in a smoker, analysis of accelerants in the blood seems to be helpful in determining the cause of death and whether inflammable were used.

Adolescent↗

PubMed1990

Changes in microvascular permeability with acceleration of edema in dog lungs.

Elevation of left atrial pressure to 25-40 mmHg causes continuous pulmonary edema formation in dog lungs. However, after 5-120 min, the rate of edema formation often increases (acceleration of edema). Acceleration of edema could be associated with an increase in microvascular membrane permeability because an increase in permeability would cause fluid to filter through the microvascular membrane more rapidly. To test the hypothesis that acceleration is associated with increased permeability, we used the continuous weight-gain technique to estimate the pulmonary microvascular membrane filtration coefficient (Kf) before and after acceleration of edema in 10 dogs. Acceleration occurred 36 +/- 38 (SD) min after elevation of left atrial pressure to 35.2 +/- 5.4 mmHg. Rate of weight gain increased from 0.47 +/- 0.17 g/min before acceleration to 0.88 +/- 0.26 g/min (P less than 0.05) after acceleration of pulmonary edema. Kf was increased from initial values of 0.058 +/- 0.027 to 0.075 +/- 0.029 ml.min-1.mmHg-1 (P less than 0.05) after acceleration. In five additional dogs we cannulated lung lymphatics and determined the lymph to plasma protein concentration ratio (CL/CP) before and after acceleration. CL/CP increased from base-line values of 0.37 +/- 0.07 to 0.44 +/- 0.06 (P less than 0.05) after acceleration. Both the increase in Kf and CL/CP data support the hypothesis that acceleration of edema is due, in part, to a slight increase in microvascular membrane permeability. However, the findings could also have been caused by an increase in interstitial conductance, washout of interstitial proteins, or alveolar flooding.

Animals↗

PubMed1991

Duration, amplitude and shape of accelerations in relation to fetal body movements in behavioral state 2F.

The relationship between fetal movements and fetal heart rate accelerations was analyzed in 34 healthy near term fetuses. Periods of coincidence 2F (C2F) with a mean duration of 34 +/- 6 minutes per fetus were selected, with a total of 463 accelerations. Nineteen percent of single body movements and 71% of compilations of movements were accompanied by an acceleration. The minimal duration of single movements associated with accelerations was 4-5 seconds. Movements with associated accelerations differed significantly in duration from movements without accelerations. The duration of accelerations was strongly correlated with the duration of movements. The amplitude of accelerations was not clearly correlated with the duration of movements, but depended on the type of movement. The shape of accelerations appeared to be dependent on the timing of the various fetal movements. In 77%, the number of notches in the accelerations was equal to the number of pauses in the movement complications. A discrepancy between notches in accelerations and pauses in movements could be explained in the majority of cases when the timing of the various movements in relation to one another was considered, or by the presence of fetal mouth movements.

Computers↗

PubMed2002

The accelerated residency program: the Marshall University family practice 9-year experience.

BACKGROUND: In 1989, the American Board of Family Practice (ABFP) approved the first of 12 accelerated residency programs in family practice. These experimental programs provide a 1-year experience for select medical students that combines the requirements of the fourth year of medical school with those of the first year of residency, reducing the total training time by 1 year. This paper reports on the achievements and limitations of the Marshall University accelerated residency program over a 9-year period that began in 1992. METHODS: Several parameters have been monitored since the inception of the accelerated program and provide the basis for comparison of accelerated and traditional residents. These include initial resident characteristics, performance outcomes, and practice choices. RESULTS: A total of 16 students were accepted into the accelerated track from 1992 through 1998. During the same time period, 44 residents entered the traditional residency program. Accelerated resident tended to be older and had more career experience than their traditional counterparts. As a group, the accelerated residents scored an average of 30 points higher on the final in-training exams provided by the ABFP. All residents in both groups remained at Marshall to complete the full residency training experience, and all those who have taken the ABFP certifying exam have passed. Accelerated residents were more likely to practice in West Virginia, consistent with one of the initial goals for the program. In addition, accelerated residents were more likely to be elected chief resident and choose an academic career than those in the traditional group. Both groups opted for small town or rural practice equally. CONCLUSIONS: The Marshall University family practice 9-year experience with the accelerated residency track demonstrates that for carefully selected candidates, the program can provide an overall shortened path to board certification and attract students who excel academically and have high leadership potential. Reports from other accelerated programs are needed to fully assess the outcomes of this experiment in postgraduate medical education.

Data Collection↗

PubMed2002

The effect of perturbation acceleration and advance warning on the neck postural responses of seated subjects.

The muscle and kinematic responses of subjects exposed to postural perturbations have been shown to vary with platform acceleration when this acceleration was covaried with platform velocity or displacement. The purpose of the current study was to isolate platform acceleration and examine its effect on the neck muscle response and head kinematics of seated subjects exposed to anterior perturbations. Thirty-six subjects (20 females, 16 males) underwent two blocks of 36 perturbations. Three different perturbations with peak accelerations of 7.7, 14.7, and 21.7 m/s(2) up to a common velocity of 0.5 m/s were used. In one block, subjects received an audible warning corresponding to the platform acceleration magnitude, and in the other block, no advance warning was given. Onset and amplitude of the sternocleidomastoid and cervical paraspinal muscle responses were measured using surface electromyography. Kinematic measures included linear and angular accelerations and displacements of the head. The results showed no differences in either the preperturbation posture or the muscle or kinematic responses between the warned and unwarned trials. Significant differences were observed in the onset and amplitude of the muscle and kinematic variables with perturbation acceleration, although these response differences were not linearly graded with perturbation acceleration. Gradation of muscle activation times has not been previously observed in postural perturbation studies, and their gradation with platform acceleration in the current study suggested that platform acceleration was a strong regulator of the reflex muscle response in postural perturbations.

Acceleration↗

PubMed2000

Role of awareness in head-neck acceleration in low velocity rear-end impacts.

Fourteen normal healthy seated and restrained young adults were delivered rear-end impacts of four intensities of acceleration. The chair was delivered a regulated and controlled pneumatic blow using a 30 cm cylinder to cause an acceleration of 0.5, 0.9, 1.1 and 1.4g. The accelerated chair was stopped suddenly by impacting the stopper at the other end of the 2 m long friction reduced track. In one set of trials, subjects were informed about the impending impact and in the other they were blindfolded and provided with loud auditory input to eliminate cues of the impact. The accelerations of the chair, shoulder and head of the participating subjects were measured triaxially and compared between levels of acceleration and expectation. The multiple analyses of variance revealed that the peak acceleration was significantly affected by the gender (P < 0.01), intensity of impact (P < 0.001), and expectation (P < 0.0001). The accelerations were significantly different in different axes (P < 0.001). A significant two-way interaction between acceleration and expectation (P < 0.03), and expectation and axes of acceleration (P < 0.02) would imply that awareness of the impending impact serves to significantly reduce the level of accelerations of head and neck.

Acceleration↗

PubMed1994

Effect of acceleration on the chest wall.

The gravitational force on the rib cage has been found to be an expiratory force of approximately 8 cmH2O. The gravitational force on the abdomen is an inspiratory force of the same magnitude. Because the compliance of the rib cage is greater than the compliance of the abdomen, it follows that gravity has a net expiratory effect on lung volume and that upward accelerations augmenting the gravitational force would have an additional expiratory effect. This conclusion is contrary to observations that functional residual capacity increases during headward accelerations in centrifuges and during intervals of upward acceleration in airplanes. We report the results of two studies of the effects of accelerations that are smaller in magnitude and of shorter duration than those studied in centrifuges and airplanes. The first was an experimental study of the effect of acceleration in an elevator. In subjects who relaxed against an occluded airway, airway pressure increased during upward accelerations and decreased during downward accelerations. The second was the modeling and analysis of the effects of the accelerations that occur during walking. The analysis predicted an initial expiratory response to the acceleration spike that occurs during footfall. The prediction agreed with data in the literature on the respiratory effect of walking. In both of these studies upward accelerations had an expiratory effect.

Acceleration↗

PubMed2005

Comparing acceleration and speed tuning in macaque MT: physiology and modeling.

Studies of individual neurons in area MT have traditionally investigated their sensitivity to constant speeds. We investigated acceleration sensitivity in MT neurons by comparing their responses to constant steps and linear ramps in stimulus speed. Speed ramps constituted constant accelerations and decelerations between 0 and 240 degrees /s. Our results suggest that MT neurons do not have explicit acceleration sensitivity, although speed changes affected their responses in three main ways. First, accelerations typically evoked higher responses than the corresponding deceleration rate at all rates tested. We show that this can be explained by adaptation mechanisms rather than differential processing of positive and negative speed gradients. Second, we inferred a cell's preferred speed from the responses to speed ramps by finding the stimulus speed at the latency-adjusted time when response amplitude peaked. In most cells, the preferred speeds inferred from deceleration were higher than those for accelerations of the same rate or from steps in stimulus speed. Third, neuron responses to speed ramps were not well predicted by the transient or sustained responses to steps in stimulus speed. Based on these findings, we developed a model incorporating adaptation and a neuron's speed tuning that predicted the higher inferred speeds and lower spike rates for deceleration responses compared with acceleration responses. This model did not predict acceleration-specific responses, in accordance with the lack of acceleration sensitivity in the neurons. The outputs of this single-cell model were passed to a population-vector-based model used to estimate stimulus speed and acceleration. We show that such a model can accurately estimate relative speed and acceleration using information from the population of neurons in area MT.

Acceleration↗

PubMed1998

Human horizontal vestibulo-ocular reflex initiation: effects of acceleration, target distance, and unilateral deafferentation.

The vestibulo-ocular reflex (VOR) generates compensatory eye movements in response to angular and linear acceleration sensed by semicircular canals and otoliths respectively. Gaze stabilization demands that responses to linear acceleration be adjusted for viewing distance. This study in humans determined the transient dynamics of VOR initiation during angular and linear acceleration, modification of the VOR by viewing distance, and the effect of unilateral deafferentation. Combinations of unpredictable transient angular and linear head rotation were created by whole body yaw rotation about eccentric axes: 10 cm anterior to eyes, centered between eyes, centered between otoliths, and 20 cm posterior to eyes. Subjects viewed a target 500, 30, or 15 cm away that was extinguished immediately before rotation. There were four stimulus intensities up to a maximum peak acceleration of 2,800 degrees/s2. The normal initial VOR response began 7-10 ms after onset of head rotation. Response gain (eye velocity/head velocity) for near as compared with distant targets was increased as early as 1-11 ms after onset of eye movement; this initial effect was independent of linear acceleration. An otolith mediated effect modified VOR gain depending on both linear acceleration and target distance beginning 25-90 ms after onset of head rotation. For rotational axes anterior to the otoliths, VOR gain for the nearest target was initially higher but later became less than that for the far target. There was no gain correction for the physical separation between the eyes and otoliths. With lower acceleration, there was a nonlinear reduction in the early gain increase with close targets although later otolith-mediated effects were not affected. In subjects with unilateral vestibular deafferentation, the initial VOR was quantitatively normal for rotation toward the intact side. When rotating toward the deafferented side, VOR gain remained less than half of normal for at least the initial 55 ms when head acceleration was highest and was not modulated by target distance. After this initial high acceleration period, gain increased to a degree depending on target distance and axis eccentricity. This behavior suggests that the commissural VOR pathways are not modulated by target distance. These results suggest that the VOR is initially driven by short latency ipsilateral target distance dependent and bilateral target-distance independent canal pathways. After 25 ms, otolith inputs contribute to the target distance dependent pathway. The otolith input later grows to eventually dominate the target distance mediated effect. When otolith input is unavailable the target distance mediated canal component persists. Modulation of canal mediated responses by target distance is a nonlinear effect, most evident for high head accelerations.

Acceleration↗

PubMed2003

Linear and angular head accelerations during heading of a soccer ball.

PURPOSE: Cognitive deficits observed in professional soccer players may be related to heading of a soccer ball. To assess the severity of a single instance of heading a soccer ball, this study experimentally and theoretically evaluated the linear and angular accelerations experienced by the human head during a frontal heading maneuver. METHODS: Accelerations were measured using a set of three triaxial accelerometers mounted to the head of each of four adult male subjects. These measurements (nine signals) were used to estimate the linear acceleration of the mass center and the angular acceleration of the head. Results were obtained for ball speeds of 9 and 12 m.s(-1) (approximately 20 and 26 mph). A simple mathematical model was derived for comparison. RESULTS: At 9 m.s(-1), peak linear acceleration of the head was 158 +/- 19 m.s(-2) (mean +/- standard deviation) and peak angular acceleration was 1302 +/- 324 rad.s(-2); at 12 m.s(-1), the values were 199 +/- 27 m.s-2 and 1457 +/- 297 rad.s-2, respectively. The initial acceleration pulses lasted approximately 25 ms. Measured head accelerations confirmed laboratory headform measurements reported in the literature and fell within the ranges predicted by the theoretical model. CONCLUSIONS: Linear and angular acceleration levels for a single heading maneuver were well below those thought to be associated with traumatic brain injury, as were computed values of the Gadd Severity Index and the Head Injury Criterion. However, the effect of repeated acceleration at this relatively low level is unknown.

Acceleration↗

PubMed2005

Relationships between hoof-acceleration patterns of galloping horses and dynamic properties of the track.

OBJECTIVE: To define relationships between hoof-acceleration patterns of galloping horses and dynamic properties of the track. ANIMALS: 8 Thoroughbred horses without lameness. PROCEDURE: Acceleration-time curves were recorded by use of accelerometers attached to each hoof as each horse galloped over the track straightaway. Four sessions were conducted for each horse, with the track surface modified by sequentially adding water before each session. These acceleration-time curves were analyzed to determine peak accelerations during the support phase of the stride. Track dynamic properties (hardness, rebound, deceleration rate, rebound rate, and penetration) were recorded with a track-testing device. Moisture content and dry density were measured from soil samples. Stepwise multiple regression was used to identify relationships between hoof-acceleration variables and track dynamic properties. RESULTS: Track rebound rate was most consistently related to hoof variables, especially through an inverse relationship with negative acceleration peaks for all hooves. Also, rebound rate was related to initial acceleration peak during propulsion of the hooves of the forelimb and the nonlead hind limb as well as to the second acceleration peak during propulsion of the lead hooves of the hind limb and nonlead forelimb. CONCLUSIONS AND CLINICAL RELEVANCE: The inverse relationship between track rebound rate and negative acceleration peaks for all hooves reflects the most important dynamic property of a track. Any factor that reduces negative acceleration of the hooves will increase stride efficiency by allowing smoother transition from retardation to propulsion and therefore may be important in determining the safety of racing surfaces.

Acceleration↗

PubMed2006

A novel wireless data acquisition system for the measurement of hoof accelerations in the exercising horse.

REASONS FOR PERFORMING STUDY: A device is needed to safely and wirelessly evaluate accelerations experienced by the horse hoof under a variety of surface conditions with the horse exercising at training or racing speeds. OBJECTIVES: To develop a miniaturised wireless data acquisition system (WDAS) which reliably records hoof accelerations and the times over which they occur in a minimally invasive manner in the exercising Thoroughbred. METHODS: The following criteria were set for device development: production of a lightweight and minimally invasive system, which provides an adequate acceleration range, appropriate frequency response to capture high speed events, and compatibility with a low power wireless telemetry system. Following device development, the WDAS was calibrated, and tested in 6 Thoroughbred horses over a variety of surfaces. RESULTS: Collection of acceleration in seven trials using 6 horses over a variety of surfaces resulted in repeatable acceleration data with respect to the overall characteristic shape of the impact profile. Impact accelerations varied with surface, ranging 34.8-191.7 g. Accelerations on take off were in a similar range, although higher in some trials. Peak impact accelerations tended to larger over the grass paddock surface, than either the indoor arena or the dirt track. During dirt track trials, accelerations on take-off were often comparably larger than those observed on impact within the same footfall. CONCLUSIONS: This study reports the development of a wireless system that successfully measures hoof acceleration in a minimally invasive manner over a variety of surface and exercise conditions. POTENTIAL RELEVANCE: The WDAS will be used in further studies to evaluate various components of the horse-racetrack interface, in an attempt to identify risk factors for musculoskeletal injury in the Thoroughbred racehorse.

Acceleration↗

PubMed2004

Acceleration in other axes affects +Gz tolerance: dynamic centrifuge simulation of agile flight.

BACKGROUND: Modern, thrust-vectored jet aircraft have the capability of developing multi-axis accelerations, especially during the performance of "supermaneuvers." These "agile" aircraft are capable of unconventional flight. The human consequences of this agile flight environment are unknown. METHODS: This multi-axis acceleration environment was studied on the Dynamic Environment Simulator gimbaled centrifuge. There were nine relaxed, unprotected subjects who were exposed to either lateral (+/- 1, +/- 2 Gy), transverse chest-to-back (+1, 2.5, or 4 Gx), or back-to-chest (-1 Gx) sustained acceleration. Positive C (+Gz) acceleration was then added beginning at 1.0 Gz by gradual onset (0.1 Gz x s(-1)) until the subjects lost nearly all of their vision. Baseline +Gz-only relaxed tolerances were measured before and after all combined Gy/Gz and Gx/Gz exposures. Heart rate, percent cerebral oxygen saturation, and cerebral blood volumes were collected during each exposure. RESULTS: Adding moderate transverse (+Gx) acceleration significantly reduced +Gz tolerance. Relaxed, unprotected +Gz tolerance was reduced approximately 0.25 G when 1.0 or 2.5 Gx was added to the increasing +Gz exposure. Adding moderate lateral Gy significantly increased +Gz tolerance. Relaxed, unprotected +Gz tolerance was increased approximately 0.5 G when +2 Gy or -2 Gy was added to the -Gz exposure. The decrease in cerebral blood volume was significantly less when +Gz was added to -1 Gx compared with the addition of +Gz to +Gx. CONCLUSIONS: Multi-axis sustained accelerations, such as those experienced during thrust-vectored aircraft maneuvers, can either enhance or reduce the +Gz tolerance of the pilot depending on the direction of the net gravitoinertial force. Gy acceleration in conjunction with Gz acceleration can enhance G tolerance. Gx acceleration in addition to Gz acceleration can reduce G tolerance.

Acceleration↗

PubMed2006

Cardio-respiratory responses evoked by transient linear acceleration.

INTRODUCTION: Predictive control of the responses to re-orientating stimuli and its interaction with vestibular signals may be an important factor in protecting against spatial disorientation. Here we evaluated the influence of stimulus predictability on the cardio-respiratory responses to transient fore-aft linear accelerations. METHODS: There were 13 normal subjects and 6 patients with bilateral loss of vestibular function who were exposed to linear acceleration of +0.26 Gx peak while seated upright and restrained on a motorized bogie. Accelerations were: (1) 'unpredictable', triggered by the experimenter either at the end of expiration or at the end of inspiration; or (2) 'predictable', triggered by the subjects pressing a button. The two conditions included false trials when nothing would happen. Respiratory frequency, electrocardiogram, and trunk acceleration were recorded. RESULTS: For unpredictable accelerations, in all subjects, the RR interval decreased within the first to second beat after acceleration onset. In normal subjects this decrease was maintained or more evident during the third, fourth, or fifth heart beat after onset. Cardiac responses were not significantly different when acceleration was triggered at the end of inspiration or at the end of expiration. Self-triggered acceleration also provoked prolonged, but attenuated, heart rate responses in healthy subjects, while responses were absent in the patients. All subjects responded with a consistent rapid inspiration to the onset of acceleration, whether predictable or not. DISCUSSION: A vestibulo-cardiac response is evoked by transient linear acceleration, independently from the phase of the breathing cycle and from the predictability of the stimulus. A vestibular signal of motion appears to be required to produce a prolonged increase in heart rate.

Acceleration↗

PubMed1992

Value of acceleration flow signals proximal to the leaking orifice in assessing the severity of prosthetic mitral valve regurgitation.

To test the value of acceleration flow signals proximal to the leaking orifice in assessing the severity of prosthetic mitral valve regurgitation, 39 consecutive patients undergoing left ventriculography were examined by Doppler color flow imaging. Acceleration flow signals proximal to the regurgitant orifice were detected in 27 of the 31 patients who had prosthetic mitral regurgitation by left ventriculography (sensitivity 87%). All four patients without acceleration flow signals had mild prosthetic mitral regurgitation by angiography. No acceleration flow signals were detected in any patient without prosthetic regurgitation by left ventriculography (specificity 100%). Individual values of the maximal area of acceleration flow signals obtained from three orthogonal planes in seven patients with mild prosthetic mitral regurgitation by angiography ranged from 0 to 17 mm2 (mean 4 +/- 6). In 8 patients with moderate prosthetic mitral regurgitation by angiography, the maximal area of acceleration flow signals ranged from 21 to 58 mm2 (mean 33 +/- 15), whereas the maximal area of acceleration flow signals in 16 patients with severe prosthetic regurgitation ranged from 20 to 173 mm2 (mean 102 +/- 41). The maximal area of the acceleration flow signals from three planes correlated well with the angiographic grade of prosthetic mitral regurgitation. There was a significant difference in the maximal area of acceleration flow signals between mild and moderate (p less than 0.001), moderate and severe (p less than 0.001) and mild and severe (p less than 0.001) prosthetic mitral regurgitation. Thus, measurement of acceleration flow signals by Doppler color flow imaging is useful in assessing the severity of prosthetic mitral regurgitation.

Bioprosthesis↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed1995

Mechanism of acceleration of antithrombin-proteinase reactions by low affinity heparin. Role of the antithrombin binding pentasaccharide in heparin rate enhancement.

The role of the sequence-specific pentasaccharide region of high affinity heparin (HAH) in heparin acceleration of antithrombin-proteinase reactions was elucidated by determining the accelerating mechanism of low affinity heparin (LAH) lacking this sequence. LAH was shown to be free of HAH (< 0.001%) from the lack of exchange of added fluorescein-labeled HAH into LAH after separating the polysaccharides by antithrombin-agarose chromatography. Fluorescence titrations showed that LAH bound to antithrombin with a 1000-fold weaker affinity (KD 19 +/- 6 microM) and 5-6-fold smaller fluorescence enhancement (8 +/- 3%) than HAH. LAH accelerated the antithrombin-thrombin reaction with a bell-shaped dependence on heparin concentration resembling that of HAH, but with the bell-shaped curve shifted to approximately 100-fold higher polysaccharide concentrations and with a approximately 100-fold reduced maximal accelerating effect. Rapid kinetic studies indicated these differences arose from a reverse order of assembly of an intermediate heparin-thrombin-antithrombin ternary complex and diminished ability of LAH to bridge antithrombin and thrombin in this complex, as compared to HAH. By contrast, LAH and HAH both accelerated the antithrombin-factor Xa reaction with a simple saturable dependence on heparin or inhibitor concentrations which paralleled the formation of an antithrombin-heparin binary complex. The maximal accelerations of the two heparins in this case correlated with the inhibitor fluorescence enhancements induced by the polysaccharides, consistent with the accelerations arising from conformational activation of antithrombin. 1H NMR difference spectroscopy of antithrombin complexes with LAH and HAH and competitive binding studies were consistent with LAH accelerating activity being mediated by binding to the same site on the inhibitor as HAH. These results demonstrate that LAH accelerates antithrombin-proteinase reactions by bridging and conformational activation mechanisms similar to those of HAH, with the reduced magnitude of LAH accelerations resulting both from a decreased antithrombin affinity and the inability to induce a full activating conformational change in the inhibitor.

Antithrombins↗

PubMed2002

A randomised phase II study of conventional versus accelerated infusional chemotherapy with granulocyte colony-stimulating factor support in advanced breast cancer.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) allows cycles of conventional bolus chemotherapy to be accelerated with reduction in treatment time and a boost in dose intensity. Theoretically, this approach could be hazardous with infusional 5-fluorouracil (5-FU) chemotherapy, since G-CSF-stimulated neutrophil proliferation would be occurring in the face of continuous S-phase active 5-FU. We performed this phase II randomised study to compare the safety, tolerability and efficacy of conventional 3-weekly epirubicin, cyclophosphamide and continuous infusional 5-FU (infusional ECF) to an accelerated 2-weekly schedule with G-CSF support, in patients with advanced breast cancer. PATIENTS AND METHODS: Twenty-seven patients were randomised. with 14 in the accelerated arm. Patients received bolus epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks (conventional arm) or every 2 weeks (accelerated arm) and 5-FU 200 mg/m2/day continuous infusion throughout. G-CSF 300 microg/day s.c. on days 10-12 was given each accelerated cycle. RESULTS: There were no treatment delays secondary to inadequate neutrophil or platelet recovery in either arm, with higher median day 1 neutrophil counts for each cycle in the accelerated arm compared with the conventional arm. Eighty-six per cent of the planned conventional chemotherapy cycles and 82% of the planned accelerated cycles were given. There were no major differences in toxicity between the arms, with the most common grade 3 toxicities being alopecia and stomatitis. Eight patients developed neutropenic sepsis (five in the accelerated arm and three in the conventional arm). Ten patients (77%) responded in the conventional arm and nine (64%) in the accelerated arm. CONCLUSIONS: Accelerated infusional ECF with limited G-CSF support is a feasible and well-tolerated regimen with rapid haematological recovery. A 50% increase in relative dose intensity of epirubicin and cyclophosphamide is achieved, while overall treatment time is reduced by 33%.

Adult↗