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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↗

PubMedDate not supplied

[Determining factors of acceleration in sustained monomorphic ventricular tachycardias in response to bursts of stimuli].

To analyse the determinants of acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid ventricular pacing, we studied 46 consecutive patients with 90 distinct ventricular tachycardias during which one or more burst of rapid pacing were delivered. Tachycardia acceleration was observed in 11 tachycardias in 8 patients. The highest incidence of acceleration was observed in patients with left ventricular dysfunction of non coronary origin. There was a non significant trend towards lower values of left ventricular ejection fraction in patients with acceleration. There were no significant differences between ventricular tachycardias with of without acceleration in respect to: clinical presentation, QRS morphology, tachycardia cycle length and treatment with antiarrhythmic drugs. The shortest cycle of bursts of rapid pacing, was lower in tachycardias with acceleration than in those without it (229 +/- 57 ms vs 283 +/- 67 ms; p = 0.006) and tachycardias with acceleration showed a lower relation between burst cycle length and tachycardia cycle length (69 +/- 9% vs 84 +/- 8%; p < 0.001). The negative predictive value of acceleration was 75% for bursts of rapid pacing with a cycle length > or = 250 ms, and 96% for values of the relation between the burst cycle length and the tachycardia cycle length > or = 70%. This parameter show a very high discriminating value with of without antiarrhythmic drugs effect. Acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid pacing depends on, the pacing rate and the relation between pacing rate and tachycardia rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

Effects of acceleration on the accuracy of MR phase velocity measurements.

Acceleration in blood flow can affect the accuracy of phase velocity measurements. Convective acceleration is due to changes in flow geometry and is independent of the time-varying acceleration caused by flow pulsatility. To analyze the effects of convective acceleration on flow velocity measurements, phase velocity measurements were obtained in steady laminar flow in the convergent segment of a 90%, hourglass-shaped stenosis phantom at a Reynolds number of 1,500. Measurements at the stenosis indicated that convective acceleration caused the measured values of average cross-sectional velocity to deviate as much as 37% from the theoretical values. The magnitude of the error could be accounted for by including the convective acceleration term in the phase shift equation. Convective acceleration effects should not be ignored in flow velocity measurements through stenoses, even when time-dependent acceleration due to flow pulsatility can be neglected.

Acceleration↗

PubMed1979

Head acceleration and psychomotor performance.

Concussion resulting from head acceleration could explain the poor survival rates in some types of accidents. Experiments have been conducted on a decelerator using a tracking task to determine whether high head acceleration could affect psychomotor performance. Human subjects were exposed to impact acceleration of O (sham), 5, 10 and 12 -Gx facing forwards. Measurements were made of the linear and angular accelerations experienced at the head and a step tracking task was used to examine psychomotor performance. Electroencephalographs were also recorded. Both the linear and angular accelerations at the head were increased at the higher levels of impact acceleration. At -5Gx there were no significant differences in psychomotor performance when compared with controls, but at -10Gx, and especially -12Gx, significant differences were found. The EEG activity did not vary significantly and no concussive effects were observed in any subject. These results suggest that impairment of psychomotor performance severe enough to jeopardise survival could be produced by high accelerations of the head, though neither linear nor angular acceleration appear to have special significance.

Acceleration↗

PubMed1990

Effect of beta adrenoceptors and thyroid hormones on velocity and acceleration of peripheral arterial flow in hyperthyroidism.

Brachial artery flow patterns were studied in 10 hyperthyroid and 10 normal subjects. Mean blood velocity and flow were evaluated by pulsed Doppler, and peak systolic acceleration was calculated by computer-assisted digitization of the instantaneous velocity curve. Compared to control subjects, hyperthyroid patients had higher velocity and flow (p less than 0.01, p less than 0.02) and higher peak systolic acceleration (p less than 0.01). In hyperthyroid patients, measurements were repeated after (1) mechanical exclusion of the hand from brachial circulation, (2) short-term beta-blocker treatment and (3) inducement of the euthyroid state. Exclusion of the hand reduced velocity and flow (p less than 0.001) but did not change peak systolic acceleration. Beta blockade induced disparate changes of velocity and flow but reduced peak systolic acceleration (p less than 0.05). In the euthyroid state, decreased blood velocity (p less than 0.01), flow (p less than 0.02) and acceleration (p less than 0.02) were observed. A hyperkinetic arterial circulation consisting of an increase in both velocity and acceleration is thus observable in hyperthyroidism. Hand exclusion showed that velocity seems to be influenced by peripheral factors while beta blockade suggests that acceleration is dependent of beta 1 adrenoceptors. Comparison between euthyroidism and hyperthyroidism indicates that both mean blood velocity and peak systolic acceleration are influenced by thyroid hormones.

Adrenergic beta-Antagonists↗

PubMed2026

Factors Associated With Accelerated Fracture Healing in Patients With Traumatic Brain Injury and Extremity Comminuted Fractures: A Retrospective Case-Control Study.

OBJECTIVE: Although traumatic brain injury (TBI) has been clinically associated with accelerated bone healing, the factors that determine which patients experience this phenomenon remain poorly defined, and previous findings are conflicting. This study aimed to investigate the clinical factors associated with accelerated fracture healing in patients with TBI combined with comminuted fractures of the limbs, so as to provide an evidence-based foundation for elucidating the clinical phenomenon of TBI-promoted fracture healing. METHODS: A retrospective case-control study design was employed. Patients between January 2020 and April 2024 with concurrent diagnoses of TBI and comminuted fractures were included. Based on radiographic findings and RUST/mRUST scores, patients were divided into an accelerated healing group (AHG) and a normal/delayed healing group (NDHG). Clinical data including demographics (age, sex, BMI), TBI characteristics (injury site, GCS score), admission laboratory indices (blood count, coagulation function, inflammatory markers), and fracture site/local soft tissue conditions, as well as functional outcomes assessed by the Short Musculoskeletal Function Assessment (SMFA) questionnaire at final follow-up were collected. Univariate analysis and multivariate logistic regression analysis were used to identify independent factors influencing accelerated fracture healing. Receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: A total of 119 patients were included, with 69 in the AHG and 50 in the NDHG. Significant differences were observed between the two groups in terms of age, BMI, GCS score, and platelet count (p < 0.05). Univariate analysis showed that age, BMI, GCS score, red blood cell count, and platelet count were associated with accelerated fracture healing (p < 0.20). Multivariate logistic regression analysis indicated that younger age (OR = 0.875, 95% CI: 0.821-0.934) and lower GCS score (indicating more severe TBI; OR = 0.490, 95% CI: 0.339-0.707) were independent predictors of accelerated fracture healing. ROC curve analysis showed that the area under the curve (AUC) for age and GCS score in predicting accelerated healing were 0.893 and 0.851, respectively. CONCLUSIONS: In patients with TBI combined with comminuted fractures, younger age and greater TBI severity (lower GCS score) are independent predictors of accelerated fracture healing. These findings assist clinicians in the early identification of patients with high healing potential to optimize treatment strategies, facilitate the early identification of high-risk patients, and provide clinical clues for further exploration of the molecular mechanisms underlying neurohumoral regulation of bone regeneration.

Humans↗

PubMed1991

Assessment of aortic regurgitation by the acceleration flow signal void proximal to the leaking orifice in cinemagnetic resonance imaging.

BACKGROUND: The proximal acceleration flow region is a laminar flow field that is located immediately upstream from the leaking orifice. The purpose of this study was to evaluate whether cinemagnetic resonance imaging can provide information regarding the proximal acceleration flow region in patients with aortic regurgitation and to analyze the relation between the area of the proximal acceleration flow delineated by cinemagnetic resonance imaging and the severity of aortic regurgitation delineated by angiography. METHODS AND RESULTS: Thirty-eight consecutive patients who underwent aortography were examined by cinemagnetic resonance imaging. The region of proximal flow acceleration was identified as a semicircular-shaped signal void in the aorta during diastole. Cinemagnetic resonance imaging detected the proximal acceleration flow region in 26 of the 30 patients who were proved to have this lesion (sensitivity, 87%). In eight patients without aortic regurgitation according to aortography, no proximal acceleration flow region was detected (specificity, 100%). The area of the acceleration flow signal void from the long-axis view was well correlated with angiographic degree of aortic regurgitation. CONCLUSIONS: Cinemagnetic resonance imaging is useful in detecting the proximal acceleration flow region and permits noninvasive assessment of the severity of aortic regurgitation.

Adult↗

PubMedDate not supplied

Accelerated graft coronary artery disease: diagnosis and prevention.

Accelerated graft coronary artery disease (CAD) has become a major factor limiting survival among long-term heart transplant survivors. Currently 14%, 37%, and 50% of patients treated with triple therapy have angiographically apparent accelerated graft CAD at 1, 3, and 5 years after transplantation. Because cardiac allografts are denervated, transplant recipients generally do not experience angina pectoris. Therefore accelerated graft CAD may present as silent myocardial infarction, congestive heart failure, or ventricular arrhythmia leading to syncope or sudden death. Noninvasive tests for CAD have been insensitive for the detection of accelerated graft CAD because of the diffuse nature of the disease. Coronary arteriographic characteristics of accelerated graft CAD are a mixture of typical focal atherosclerotic lesions and unusual diffuse, concentric, and longitudinal narrowing prominent in middle to distal coronary vessels, with distal vessel obliteration and lack of collateral vessel formation. The presence and severity of accelerated graft CAD may be underestimated by routine angiography because of its diffuse and concentric nature. Quantitative arteriography has become an important technique to assess the progression of accelerated graft CAD. Intravascular ultrasound imaging can detect even earlier development of intimal thickening. CAD risk factor modification has had little impact on the overall incidence. We initiated a randomized study of diltiazem versus no calcium blocker to determine if this may prevent accelerated graft CAD. Patients have undergone early postoperative and annual quantitative coronary angiography since inception of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗

PubMed1979

The velocity response of vestibular nucleus neurons during vestibular, visual, and combined angular acceleration.

In alert Rhesus monkeys neuronal activity in the vestibular nuclei was measured during horizontal angular acceleration in darkness, acceleration of an optokinetic stimulus, and combined visual-vestibular stimulation. The working ranges for visual input velocity and acceleration extend up to 60 degrees/s and 5 degrees/s2. The corresponding working range for vestibular input acceleration is wider and time-dependent. During combined stimulation, that is acceleration of the monkey in the light, a linear relation between neuronal activity and velocity could be established for all neurons. Type I vestibular plus eye movement neurons displayed the greatest sensitivity and had a small linear range of operation. Other vestibular neurons were less sensitive but had a larger range of linear response to different values of acceleration. Accelerating the animal and visual surround, simultaneously but in opposite directions, results in neuronal activity proportional to relative velocity over a limited range.

Acceleration↗

PubMed2026

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans↗

PubMedDate not supplied

[Effect of acceleration on the sugar content of rabbit cerebrospinal fluid].

The sugar content in the liquor of rabbits exposed to accelerations ranging from several minutes to several hours was studied. The animals were accelerated at 3 g in a centrifuge with a radius of 55 cm and a velocity of 70 rpm, in the Khilov's swing and in a rotating device simulating angular accelerations. The liquor was sampled by the suboccipital puncture and the sugar content was measured according to Hagedorn-Jensen. A statistically significant increase in the sugar content was noted after every exposure to accelerations of alternating signs than with accelerations of a constant value. The experiments on labyrinth-ectomized animals showed a certain effect of the vestibular analyzer on the carbohydrate metabolism. However, when the equilibrium function reached compensation, the sugar content in the liquor returned to the pretest level. Therefore, this reaction involves not only the vestibular system but also the optic, proprio- and interoceptive afferent systems. A comparison of the intracysternal and intramuscular injections of epinephrine points to the central (in contrast to the hematogenic) nature of an increase in the sugar content during the first minutes of acceleration. The electric stimulation of the anterior and posterior hypothalamus by means of implanted electrodes produced the same elevation of the liquor sugar as accelerations. It can be postulated that afferent impulses from the analyzer systems reach the hypothalamic centers, thus exciting the autonomic system and, first of all, the sympathic system.

Acceleration↗

PubMed1992

The relationship between head and neck anthropometry and kinematic response during impact acceleration.

Research on the effects of impact acceleration on the body, primarily the head and neck, has been conducted at the U.S. Naval Biodynamics Laboratory for nearly two decades. Over 150 Navy enlisted men have been subjected to impact acceleration on a sled propelled by a nitrogen-powered horizontal accelerator. Their head and neck kinematic responses during the experimental impact were measured and stored in automated data bases. Similarly, anthropometric measurements were recorded for these subjects. To investigate the relation between head and neck anthropometry and response to impact acceleration, tests involving 15 subjects were selected. A strong relation was found between head and neck anthropometry and linear acceleration of the head along the Z axis. Lesser correlations were determined between the anthropometric measurements and linear acceleration along the X axis and angular acceleration about the Y axis. These findings are potentially applicable to areas such as aircrew selection, physical training and protective equipment development.

Acceleration↗

PubMedDate not supplied

Effects of +Gz acceleration on human body systems as a form of training based of physiological data evaluation.

Twenty-five men with decreased acceleration tolerance limits were subjected to two weeks centrifuge training, in which selected characteristics of +Gz acceleration (head-feet directed) were applied. The training loads were controlled basing on the responses of blood flow velocity and heart rate. The results show that the human centrifuge training in which the graded loads are based on measurement of these parameters, increases acceleration tolerance limits. It is also demonstrated that the human centrifuge training methods can be used in pilots after convalescence period or on finding lowered acceleration tolerance produced by other causes. The physical and physiological methods of increasing acceleration tolerance limits (ATL) consist some of the most important and urgent problems of today to be solved in modern military aviation. This demand is produced not only by the systematically increasing requirements as to the highest health performance of the military pilot, but also by the enormous costs of the flying equipment and training. In the group of different methods of increasing ATL, the human centrifuge training is an open problem. The available literature presents only a few reports in which the +Gz acceleration (i.e. head-pelvis directed) was used as the loading stimulus in pilots' training. The reasons for the lack of interest in this direction of examination include: easily developed decompensation of the circulatory system; cummulated effects of acceleration, and lack of optimal criteria to evaluate the body systems loads. Moreover, the positive effects of training could be baffled by the above mentioned factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗

PubMed1991

Ventricular tachycardia and accelerated ventricular rhythm presenting in the first month of life.

Fourteen infants aged less than 1 month presented to our institution during the last 22 years with ventricular tachycardia (VT) or accelerated ventricular rhythm and a structurally normal heart. In 2, VT was associated with long QT syndrome. Both are alive on beta-blocker therapy, 1 with an implanted pacemaker. Twelve infants had accelerated ventricular rhythm, and 2 of these died in the first 2 months of life of unrelated conditions. The other 10 are alive at a median age of 4 years (range 2 months to 11 years), and none were lost to follow-up. Hemodynamic compromise did not occur with accelerated ventricular rhythm. The ventricular rate was very close to the sinus rate in all 12, less than 12% above the sinus rate. The mean QRS duration during accelerated ventricular rhythm was 92.5 ms, and averaged twice the QRS duration during sinus rhythm. Fusion beats were seen in all 12, and there was atrioventricular dissociation with capture beats in 10. In 2, ventriculoatrial conduction was present. Treatment was attempted in 5 of the 10 survivors with accelerated ventricular rhythm, and was thought to be successful in 4. Treatment was later successfully withdrawn in all 5, so that all 10 survivors were free of accelerated ventricular rhythm and were not receiving antiarrhythmic medications at last follow-up. Because of the excellent long-term outcome and the lack of hemodynamic compromise during the rhythm, it seems reasonable to withhold antiarrhythmic therapy in infants with accelerated ventricular rhythm and await resolution of the rhythm.

Anti-Arrhythmia Agents↗

PubMed1992

Physiologic concentrations of inorganic phosphate accelerate fructosamine synthesis.

The effect of physiologic concentrations of inorganic phosphate (Pi) on fructosamine (FRA) synthesis was studied. After 75 g oral glucose administration (OGTT), 'delta FRA/24 h', defined as delta FRA after incubating serum or other specimens at 37 degrees C for 24 h after adding 1000 mg/dl glucose, was significantly decreased in parallel to the decrease of plasma Pi concentrations. 'The FRA index', defined as the FRA value divided by the corresponding glucose concentration, both at fasting, correlated significantly with plasma Pi concentrations. In vitro incubation of serum total protein (TP), albumin (ALB), gamma-globulin (GLB), free lysine (Lys), and free valine (Val) with glucose at different concentrations of Pi showed a Pi-dependent increase of FRA synthesis throughout 48 h of incubation. The accelerating effect of 5 mg/dl Pi on FRA synthesis from TP, ALB, GLB, Lys, and Val at pH 7.4 was, respectively, as great as 48, 20, 24, 13 or 25% of those without Pi. Increase of pH from 6 to 10 logarithmically increased delta FRA/24 h in contrast to a logarithmic decrease of the accelerating effect of Pi on delta FRA/24 h. These data show that physiologic concentrations of Pi accelerate protein glycation by accelerating dehydrogenation during the Amadori rearrangement through the negative charge of Pi. Because this accelerating effect of physiologic Pi presumably exists in vivo, Pi concentration must be taken into account as an accelerating factor for FRA synthesis in evaluating diabetic control, and further studies must be carried out to elucidate whether hyperphosphatemia accelerates glycation-induced diabetic complications.

Adult↗

PubMed1991

Accelerated repopulation: friend or foe? Exploiting changes in tumor growth characteristics to improve the "efficiency" of radiotherapy.

Accelerated repopulation (rapid multiplication of surviving clonogens) during a course of radiation therapy may contribute to local failure. This possibility has prompted accelerated treatment programs in an attempt to reduce overall treatment time, thereby minimizing the impact of repopulation. However, accelerated dose delivery at the start of treatment may not be advantageous since many of the tumor cells are likely to be hypoxic (non-cycling cells) and therefore relatively radioresistant. Conversely, accelerated treatment is likely to be most helpful later in treatment when the tumor has shrunk and accelerated repopulation of clonogens is a dominant factor. A series of calculations are presented that stimulate changes in tumor size, clonogen number, clonogen repopulation, and growth fraction during a course of fractionated radiation treatments for an idealized 2 cm diameter spherical tumor. The efficiency of each fraction of radiation is calculated for different radiation fractionation schemes. Efficiency is defined as the change in Log clonogen number (reflecting cell death due to radiation minus repopulation that has occurred during the interval between fractions) per Gy. These calculations suggest that relatively low total daily doses (approximately 2 Gy) are most efficient early in treatment. Higher daily doses are less efficient since the growth fraction is relatively low at the start of treatment. Later in treatment, as the tumor shrinks and the growth fraction approaches 1, accelerated repopulation becomes a major problem and higher total daily doses are more efficient. At this point, accelerated hyperfractionation should be used to increase the daily dose without exposing normal tissues to high fraction sizes. Thus, changes in tumor growth characteristics are exploited and dose delivery can be optimized by escalating daily irradiation doses during a course of fractionated irradiation. Strict interpretation of these conclusions must be tempered by the various assumptions and uncertainties included in this model. The concept of efficiency is useful since it reflects the competing effects of clonogen repopulation and radiation induced clonogen sterilization.

Cell Division↗

PubMed2025

Developmental timing of index trauma exposure and accelerated epigenetic aging in United States military veterans.

Trauma exposure has been linked to accelerated GrimAge, an epigenetic biomarker of premature morbidity and mortality. Building on this evidence, the present study examined whether the type and timing of index trauma exposure are differentially associated with accelerated GrimAge. Participants were 873 European American male United States military Veterans from the National Health and Resilience in Veterans Study. We investigated associations between self-reported age at index trauma, index trauma type (interpersonal violence, non-interpersonal trauma, or loss/instability/other), and accelerated GrimAge, operationalized as GrimAge exceeding chronological age by five or more years. Results revealed that interpersonal violence was associated with three-fold greater odds of accelerated GrimAge compared to other trauma types. Age at index trauma was not independently associated with accelerated GrimAge. However, we observed a significant interaction between trauma type and its developmental timing, even after adjusting for index trauma recency, cumulative trauma burden, and other potential confounders. Specifically, Veterans who were older at the time of exposure to interpersonal violence or trauma involving loss or instability had higher odds of accelerated GrimAge. In contrast, exposure to non-interpersonal trauma was more strongly associated with accelerated GrimAge when it occurred at younger ages. These results indicate that trauma type and timing jointly influence epigenetic aging in Veterans, highlighting the need for tailored interventions that address specific trauma characteristics to reduce associated long-term health risks in this population.

Humans↗