Slow Responding Research Articles

High stakes slow responding, but do not help overcome Pavlovian biases in humans.

"Pavlovian" or "motivational" biases are the phenomenon that the valence of prospective outcomes modulates action invigoration: the prospect of reward invigorates actions, while the prospect of punishment suppresses actions. Effects of the valence of prospective outcomes are well established, but it remains unclear how the magnitude of outcomes ("stake magnitude") modulates these biases. In this preregistered study (N = 55), we manipulated stake magnitude (high vs. low) in an orthogonalized Motivational Go/NoGo Task. We tested whether higher stakes (a) strengthen biases or (b) elicit cognitive control recruitment, enhancing the suppression of biases in motivationally incongruent conditions. Confirmatory tests showed that high stakes slowed down responding, especially in motivationally incongruent conditions. However, high stakes did not affect whether a response was made or not, and did not change the magnitude of Pavlovian biases. Reinforcement-learning drift-diffusion models (RL-DDMs) fit to the data suggested that response slowing was best captured by stakes prolonging the non-decision time. There was no effect of the stakes on the response threshold (as in typical speed-accuracy trade-offs). In sum, these results suggest that high stakes slow down responses without affecting the expression of Pavlovian biases in behavior. We speculate that this slowing under high stakes might reflect heightened cognitive control, which is however ineffectively used, or reflect positive conditioned suppression, i.e., the interference between goal-directed and consummatory behaviors, a phenomenon previously observed in rodents that might also exist in humans. Pavlovian biases and slowing under high stakes may arise in parallel to each other.

The development of modal intuitions: A test of two accounts.

Young children, unlike adults, deny that improbable events can happen. We test two accounts explaining this developmental shift. The development = reflection account posits that this shift is driven by an emerging ability to reflect on modal intuitions. In contrast, the development = intuition account posits that this shift is driven by changes in modal intuitions themselves, due to age-related changes in what people know and how they sample their knowledge and memories. These accounts make competing predictions about how long children and adults should take to make possibility judgments. In Experiment 1, we asked 123 children (39 5-year-olds, 42 7-year-olds, 42 9-year-olds; 49.60% White) and 40 adults (50% White) to judge the possibility of 78 ordinary, improbable, and impossible events and recorded their response times. In Experiment 2, we tested an additional 52 adults (42.32% White) who were under speeded conditions and thus less able to reflect before responding. Our results favor the development = intuition account. At all ages, people judged improbable events more slowly than ordinary or impossible events, and slow responding did not consistently predict affirmation over denial. Further, adults' possibility judgments did not change under speeded conditions. We also fit a drift-diffusion model to our data, which suggested that adults and children may sample different kinds of knowledge when generating intuitions. Our findings suggest that possibility judgments are often driven by modal intuitions with little reflection, and that a developmental shift in what children know and how knowledge is retrieved can explain why these intuitions change over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genomic Determinants of Therapy Response in ETV6::RUNX1 Leukemia

ETV6::RUNX1 leukemia is the second most common childhood B-cell acute lymphoblastic leukemia subtype. Although it has a low overall relapse risk, a significant proportion of relapses occur within this subtype due to its relatively high incidence. No consistent genomic biomarkers have been identified that predict therapy response beyond early therapy response as measured by minimal residual disease at the end of induction. In this study, our aim was to use multiomic data from 175 ETV6::RUNX1 leukemias treated according to the NOPHO ALL2000 and ALL2008 protocols to identify genomic features that predict therapy response at presentation. Cases were classified into three responder groups based on MRD at end-of-induction (EOI) therapy: fast responders with negative MRD, intermediate responders with positive but <0.1% MRD, and slow responders with >0.1% MRD. Response data was also collected at mid-induction (day 15) and end-of-consolidation (EOC), when available. Diagnostic and remission DNA were analyzed using array-based copy number data (n=142) or whole genome sequencing (WGS) (n=33), and diagnostic bulk RNA sequencing (n=51) was complemented with single cell multiomics (RNA, surface protein and VDJ sequencing) data from both healthy (n=8) and leukemic bone marrow cells upon chemotherapy (n=8). Overall, the frequency of somatic genetic changes was not significantly associated with treatment response suggesting that genetic diversification through elevated random mutagenesis events may not underlie the drug resistant phenotype. However, analysis of mutational signatures revealed that fast-responding leukemic blasts frequently exhibited the APOBEC mutational signature and had higher cell cycle activity (Figure 1A). Accordingly, we show that expression of A3B is highly specific to cycling cells also in healthy bone marrow hematopoietic progenitor cells, pro- and pre-B cells. We also examined RAG-mediated genetic instability that manifests in focal structural variations and has highest activity in ETV6::RUNX1leukemia (Figure 1B). We confirmed several recurrent RAG off-target sites, including significant enrichment of the known risk locus TBX1LR1 in slow responding cases. Strikingly, slow-responding leukemias had also frequent rearrangements in the immunoglobulin kappa genes and the kappa-deleting elements, despite their pro-B-like transcriptome state upon diagnosis. Based on the single cell multiomics profiles, we found that upon treatment the blast phenotype shifts towards an immature-B-like transcriptome, with concomitant expression of Ig light chains with productive sequence, thereby permitting activation of BCR signaling that provides a survival advantage. At CNV level, we found that the chromosomal alterations related to the translocation event associated with treatment response. Specifically, slow responders had more often the amplification of der(21)t(12;21) chromosome, impacting expression of USP5, TIGAR and SLC2A3, associated in earlier studies to chemoresistance and tumorigenesis. In comparison, fast responders were often missing a region of chromosome 12p with lower expression of several genes including oncogenic KRAS. In summary, combining multiomic and response data, we characterized genetic alterations and mutational processes that affect the treatment response in ETV6::RUNX1leukemia. Our findings highlight the genetic and transcriptomic heterogeneity of this common pediatric leukemia subtype and its implications for treatment sensitivity, paving the way for better classification of the disease at presentation.

Conflict-monitoring theory in overtime: Is temporal learning a viable explanation for the congruency sequence effect?

In interference tasks (e.g., Stroop, 1935), congruency effects are larger following a congruent versus an incongruent trial. This "congruency sequence effect" has been traditionally explained in terms of a conflict-monitoring mechanism that focuses attention toward relevant information when conflict has recently been experienced. More recently, it has been suggested that effects of this sort result from differences in the temporal expectancies formed following congruent trials (fast responding) versus incongruent trials (slow responding). Evidence supporting this "temporal-learning" account was recently reported for a similar effect, the finding that congruency effects are larger in a mostly congruent list than in a mostly incongruent list. That is, consistent with the idea that this "proportion-congruent effect" is based on different temporal expectancies following congruent versus incongruent trials in interference tasks, the proportion-congruent effect was eliminated on normal (i.e., immediate-response) trials when temporal expectancies were equated by requiring a delayed response on the prior trial. In two experiments, we examined whether this delayed-response procedure would have a similar impact on the congruency sequence effect. Consistent with the temporal-learning account (but not inconsistent with conflict-monitoring accounts), the congruency sequence effect on immediate-response trials was eliminated when the previous trial required a delayed response. However, no evidence supporting the temporal-learning account emerged from reanalyses of experiments requiring only immediate responses in which the response latency in the previous trial functioned as the temporal-expectancy index. Overall, the present results and analyses do not provide much evidence favoring the temporal-learning account over conflict-monitoring accounts of the congruency sequence effect. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Strategies of feigning mild head injuries related to validity indicators and types of coaching: Results of two experimental studies

Objective In this paper, we analyzed differences between uncoached, symptom-coached, and test-coached simulators regarding strategies of feigning mild head injuries. Method Healthy undergraduates (n = 67 in the first study; n = 48 in the second study), randomized into three simulator groups, were assessed with four experimental memory tests. In the first study, tests were administered face-to-face, while in the second study, the procedure was adapted for online testing. Results Online simulators showed a different approach to testing than face-to-face participants (U tests < 920, p < .05). Nevertheless, both samples favored strategies like memory loss, error making, concentration difficulties, and slow responding. Except for slow responding and concentration difficulties, the favorite strategies correlated with validity indicators. In the first study, test-coached simulators (m = 4.58–5.68, SD = 2.2–3) used strategies less than uncoached participants (m = 5.25–5.88, SD = 2.26–2.84). In the second study, test-coached participants (m = 3.8–5.6, SD = 1.51–2.2) employed strategies less than uncoached (m = 6.21–7.29, SD = 1.25–1.85) and symptom-coached participants (m = 6.14–6.79, SD = 1.69–2.76). Discussion Similarities and differences between online and face-to-face assessments are discussed. Recommendations to associate heterogeneous indicators for detecting feigning strategies are issued.

Acarid Suction Cup‐Inspired Rapid and Tunable Magnetic Adhesion

AbstractAdhesion appears in nature as a kind of clinging strategy for living creatures to survive in a complex environment. Nevertheless, the artificial counterpart applications are limited by many factors, such as slow responding rate and high driving voltage. In this paper, a novel magnetic adhesion achieved by the actuation of Ecoflex embedded with iron particles is presented, which is demonstrated by a magnetic suction cup (MSC) that can switch the adhesion state within 500 ms. Compared with suction cups made of the dielectric elastomer in existing literature, the present work's driving voltage is safe for humans. Furthermore, a mechanical model is developed and verified to optimize the design of the MSCs. By applying an altering magnetic field, the adhesive force varying with time exhibits complex waveforms such as sinusoidal wave, triangle wave, square wave, and even pulse wave can be achieved. For some situations that large adhesion force is not necessarily considered while the adhesion requires to be accurately and quickly controlled, such as transfer printing and intelligent sensing, the magnetic adhesion demonstrated in this article will enrich the future available applications.

Dissociating Slow Responses From Slow Responding.

Increased Intra-Subject Variability (ISV) is a candidate endophenotype of ADHD. ISV’s relationship with response speed is highly relevant for ADHD as patients are highly variable but typically no slower than controls. This brief report addresses the relationship between variability and speed by employing dimensional analyses for differentiated performance measures, with a particular focus on the ex-Gaussian measures, across relevant ADHD studies and in young healthy adults (N = 70). For both patients with ADHD and healthy adults, we found that reaction time standard deviation and mean reaction time were strongly correlated, thus failing to dissociate, but ex-Gaussian tau (τ) shared only little variance with Gaussian mu (μ), thus dissociating slow responses (τ) from response speed or—if given—slow responding (μ). Our results highlight the utility of employing the ex-Gaussian measures to disentangle ISV and speed, particularly for ADHD data as patients make more slow responses but are not overall slower than typical controls.

Different bacterial host-based lux reporter array for fast identification and toxicity indication of multiple metal ions

Although luminescent bacteria-based bioluminescence inhibition assay has been widely used in the toxicity assessment of environmental pollutants, the response of a luminescent bacterium usually lacks specificity to a target analyte. Recently, some specific analyte inductive promoters were fused to the lux genes for the purpose of selective bioluminescent sensing, and suits of specific promoters were fused to lux genes to compose a bioluminescent array sensor for simultaneous identification of multiple analytes. However, specific promoter-based methods still suffer from drawbacks including limited selectivity, slow responding time, expensive to construct different promoters involved plasmids, and laborious to find new promoters. Herein, we proposed a novel strategy to construct a lux reporter array sensor by directly transforming the natural lux genes in different bacterial hosts without the involvement of any specific promoters. Due to the distinct pathways of signal production, the responding time of the current different bacterial host (DBH)-based lux reporter array has nearly an order of magnitude faster than with specific promoter-based methods. The DBH-based lux reporter array was successfully used for simultaneous identification, quantification, and toxicity/bioactivity assessment of multiple metal ions. Obviously, all the chemical synthetic material-based metal ion sensing methods cannot simultaneously achieve analysis and toxicity evaluation. This approach possessed additional advantages of facile construction, easy operation, high selectivity, fast response, and strong adaptability to other analytes. A different bacterial host-based lux reporter array was established for simultaneous analysis and toxicity assessment of multiple metal ions.

Activation of Subthalamic Nucleus Stop Circuit Disrupts Cognitive Performance.

Much evidence supports a fundamental role for the subthalamic nucleus (STN) in rapidly stopping behavior when a stop signal or surprising event occurs, but the extent to which the STN may be involved in stopping cognitive processes is less clear. Here, we used an optogenetic approach to control STN activity in a delayed-match-to-position (DMTP) task where mice had to recall a response location after a delay. We first demonstrated that a surprising event impaired performance by both slowing the latency to respond and increasing the rate of errors. We next showed that these effects could be mimicked by brief optogenetic activation of the STN. Further, inhibiting STN during surprise blocked surprise-induced slowing, although without changing surprise-induced errors. These data are consistent with the hypothesis that STN is recruited by surprise to slow responding and that this can also interrupt cognitive processes. Under normal conditions STN-mediated stopping of behavior may slow or stop ongoing cognition to facilitate cognitive reorienting and adaptive responses to unexpected sensory information, but when malfunctioning, it could produce pathologies related to over-rigidity or increased distractibility.

Investigating Response Patterns Across Surveys: Do Respondents Show Consistency in Undesirable Answer Behaviour over Multiple Surveys?

The relation between answer behaviour and measurement error has been studied extensively. Answer behaviour may be considered undesirable, like answering ‘don’t know’ or ‘won’t tell’. It is not clear to what degree undesirable answer behaviour from the same respondents is present across different surveys. In this study, we investigated to what extent respondents show undesirable answer behaviours consistently over multiple surveys. First, we investigated to what extent the answer behaviours occurred in ten large general population surveys of CentERdata and Statistics Netherlands. Second, we explored the respondent variances and respondent-survey interaction variances to obtain an indication for respondent consistency for each answer behaviour. The results showed that respondents only occasionally give ‘don’t know’– and ‘won’t tell’-answers. An indication for respondent consistency was found for fast responding, slow responding, and ‘won’t tell’-answers in particular. We recommend follow-up research to investigate the relation between respondent characteristics and consistent answer behaviour.

Initial analyses of a phase I/II trial of durvalumab (D) plus tremelimumab (T) and stereotactic body radiotherapy (SBRT) for oligometastatic head and neck carcinoma.

6531 Background: PD-1/PD-L1 +/- CTLA-4 blockade in head-and-neck carcinoma (HNSCC) has shown signs of clinical activity. SBRT aims to reduce tumor burden and perhaps be immune-stimulatory. This analysis seeks to assess the safety and efficacy signal of the triple treatment combination (TTC) consisting of SBRT sandwiched between cycles of D (αPD-L1) and T (αCTLA-4) in oligometastatic (2-10) HNSCC. Methods: This is a single arm multi-institutional phase I/II trial (NCT03283605). D (1500 mg) and T (75 mg) were given for 4 monthly cycles, followed by monthly D. SBRT to 2-5 lesions was administered during cycle 2. The median prescribed and maximum SBRT doses were 40 Gy (range:18-50) and 49 Gy (range:28-61), respectively, given in 3-5 fractions. Global health status was derived from EORTC QLQ C30 questionnaires. Results: At data cut-off (Dec 31, 2019), 20 patients were recruited, of which 16 had a study treatment and were analyzed. Table describes the patient characteristics. There were 1 CTCAE V5.0 Grade 2 and 1 Grade 3 (both GI) serious adverse event (SAE) attributable to D and T. Two patients had unrelated SAEs (1 Grade 3-hypercalcemia and 1 Grade 5-GI). The Grade 5 SAE was a gastric hemorrhage that occurred the night of the first D + T infusion. There was no Grade 3+ AE secondary to SBRT. Thus, SBRT did not add to the 2/16 patients who had D + T related SAEs. Global health status scores did not differ statistically between baseline (75) and cycle 3 (73). Of the 14 patients that received SBRT, 7 patients had RECIST target lesions untreated by SBRT. The best responses for these 7 patients were: 1 CR, 3 PR, and 3 SD. When SBRT treated lesions are included and analyzed per RECIST (n = 14), there were 9 PR, 3 SD and 2 PD. The estimated median progression free survival was 7.2 months. Conclusions: The first 16 evaluable patients demonstrated tolerable profiles to the TTC (D + T + SBRT) for the treatment of oligometastatic (≤10 lesions) HNSCC. Best response rates were encouraging and could be due to the addition of SBRT during immunotherapy that served to either stimulate the immune system or annihilate slow responding or immunotherapy resistant lesions. Smaller overall tumor burden and 7/16 patients being treated in first line could also have contributed to better results. Clinical trial information: NCT03283605 . [Table: see text]

T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol.

The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD ≥ 5% on day 29 or ≥0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.

The development of fast and slow inferential responding: Evidence for a parallel development of rule-based and belief-based intuitions.

Dual process theories postulate the existence of two levels of processing, Type 1, which uses belief-based cues to make very rapid inferences, and Type 2, which uses more conscious, working memory-based processes that are, in principle, capable of making rule-based judgments. There is a common assumption that Type 1 processes are more rapidly produced, while Type 2 processes take more time. Evidence for this assumption is mixed. Recently, Newman, Gibb, and Thompson (Journal of Experimental Psychology: Learning, Memory, and Cognition, 43(7): 1154, 2017) have provided clear evidence that very fast responses use a combination of both belief-based and rule-based cues. In these studies, we initially replicated this basic result with adults using a different methodology and extended them to examine in greater detail patterns of change with restricted time. The results also show the same combination of rule-based and belief-based cues in fast responses, and suggest that time constraints differentially affect each form of cue. We then examined the developmental pattern of both fast and slow responding. Children aged between 8 and 10 years of age were examined using the methodology of the initial study. Results show that both developmental patterns and the effect of reduced time on children produce parallel changes in both belief-based and rule-based responding. These results suggest the existence of two simultaneously developing processes, consistent with a dual-strategy model of reasoning.

Dissociating top-down and bottom-up temporal attention in Down syndrome: A neurocostructive perspective

Recent studies suggest that both top-down and bottom-up temporal orienting (TO) of attention are established early and show stable trajectories in typical development. Yet, no evidence is available about atypical development of TO. In the present study, we first investigate the interplay between top-down and bottom-up temporal attention mechanisms in Down Syndrome (DS). Children and adolescents with DS (n = 33) and typically developing individuals matched to children with DS by either chronological (TD-CA; n = 33) or mental age (TD-MA; n = 31) performed a simple cued reaction time designed to assess top-down (endogenous TO) and bottom-up (foreperiod and sequential effect) temporal attention. Mean task accuracy was on average lower and more variable in the DS group than controls and it was predicted by both verbal and non-verbal ability. A subsample of “high-performing” children, showing comparable task speed and higher accuracy (≥65%), was then extracted from each group to test the presence of top-down and bottom-up temporal attention while limiting possible floor effects and overly slow responding. While the control groups showed both top-down and bottom-up TO effects, only the latter were present in DS group. Consistent with a neuroconstructivist account, this study identifies an atypical domain-general cognitive mechanism, temporal orienting of attention, that may constrain the build-up of domain-specific skills in DS, and is for investigation in other atypically developing groups.

Human instrumental performance in ratio and interval contingencies: A challenge for associative theory.

Associative learning theories regard the probability of reinforcement as the critical factor determining responding. However, the role of this factor in instrumental conditioning is not completely clear. In fact, free-operant experiments show that participants respond at a higher rate on variable ratio than on variable interval schedules even though the reinforcement probability is matched between the schedules. This difference has been attributed to the differential reinforcement of long inter-response times (IRTs) by interval schedules, which acts to slow responding. In the present study, we used a novel experimental design to investigate human responding under random ratio (RR) and regulated probability interval (RPI) schedules, a type of interval schedule that sets a reinforcement probability independently of the IRT duration. Participants responded on each type of schedule before a final choice test in which they distributed responding between two schedules similar to those experienced during training. Although response rates did not differ during training, the participants responded at a lower rate on the RPI schedule than on the matched RR schedule during the choice test. This preference cannot be attributed to a higher probability of reinforcement for long IRTs and questions the idea that similar associative processes underlie classical and instrumental conditioning.

Novel Design Integrating a Microwave Applicator into a Crystallizer for Rapid Temperature Cycling. A Direct Nucleation Control Study.

The control of nucleation in crystallization processes is a challenging task due to the often lacking knowledge on the process kinetics. Inflexible (predetermined) control strategies fail to grow the nucleated crystals to the desired quality because of the variability in the process conditions, disturbances, and the stochastic nature of crystal nucleation. Previously, the concept of microwave assisted direct nucleation control (DNC) was demonstrated in a laboratory setup to control the crystal size distribution in a batch crystallization process by manipulating the number of particles in the system. Rapid temperature cycling was used to manipulate the super(under)saturation and hence the number of crystals. The rapid heating response achieved with the microwave heating improved the DNC control efficiency, resulting in halving of the batch time. As an extension, this work presents a novel design in which the microwave applicator is integrated in the crystallizer, hence avoiding the external loop though the microwaves oven. DNC implemented in the 4 L unseeded crystallizer, at various count set points, resulted in strong efficiency enhancement of DNC, when compared to the performance with a slow responding system. The demonstrated crystallizer design is a basis for extending the enhanced process control opportunity to other applications.

When attention wanders: Pupillometric signatures of fluctuations in external attention

Attention is not always directed to events in the external environment. On occasion our thoughts wander to people and places distant from the here and now. Sometimes, this lack of external attention can compromise ongoing task performance. In the current study we set out to understand the extent to which states of internal and external attention can be determined using pupillometry as an index of ongoing cognition. In two experiments we found that periods of slow responding were associated with elevations in the baseline pupil signal over three and a half seconds prior to a behavioural response. In the second experiment we found that unlike behavioural lapses, states of off-task thought, particularly those associated with a focus on the past and with an intrusive quality, were associated with reductions in the size of the pupil over the same window prior to the probe. These data show that both states of large and small baseline pupil size are linked to states when attention is not effectively focused on the external environment, although these states have different qualities. More generally, these findings illustrate that subjective and objective markers of task performance may not be equivalent and underscore the importance of developing objective indicators that can allow these different states to be understood.

Using Variable Interval Reinforcement Schedules to Support Students in the Classroom: An Introduction With Illustrative Examples

When behaviors are reinforced with a variable interval reinforcement schedule, reinforcement is available only after an unknown period of time. These types of reinforcement schedules are most useful for reinforcing slow and steady responding and for differentially reinforcing behaviors that are incompatible with some problematic behaviors. This review helps define variable interval reinforcement schedules, uses the example of a strategy to manage thumb-sucking behavior to illustrate the implementation of these schedules, and describes potential applications in school and clinical settings.

Nonlinear control of triple inverted pendulum based on GA–PIDNN

The triple inverted pendulum is a nonlinear, dynamic and unsteady system. The traditional control methods of triple inverted pendulum have problems of limited control accuracy, slow responding. This kind of pendulum system is difficult to control due to the inherent instability, nonlinear behavior and difficultly in establishing a precise mathematical model. In addition, the back-propagation (BP) algorithm has the shortage of easy trapped in local minimum. The triple inverted pendulum control based on GA–PIDNN is proposed. The PID neural network (PIDNN) is a new kind of feedforward multi-layer network. Besides multi-layer forward networks traditional merit, such as approach the ability proceed together the calculation nonlinear transformation, its middle layer has the proportional (P) integral, (I) derivative, (D) dynamic characteristic. Genetic algorithm (GA) has good parallel design structure and characteristics of global optimization. The nonlinear identification model is established, and controller is designed via GA–PIDNN based on the combination of the merits GA and PIDNN in the research of triple inverted pendulum. In simulation, through the comparative study of GA–PIDNN and PIDNN optimized by BP (BP–PIDNN), simulations results show that GA is more accurate and effective.

TH-C-18A-09: Exam and Patient Parameters Affecting the DNA Damage Response Following CT Studies

Purpose: To identify exam and patient parameters affecting the biological response to CT studies using in vivo and ex vivo blood samples. Methods: Blood samples were collected under IRB approval from 16 patients undergoing clinically-indicated CT exams. Blood was procured prior to, immediately after and 30minutes following irradiation. A sample of preexam blood was placed on the patient within the exam region for ex vivo analysis. Whole blood samples were fixed immediately following collection and stained for γH2AX to assess DNA damage response (DDR). Median fluorescence of treated samples was compared to non-irradiated control samples for each patient. Patients were characterized by observed biological kinetic response: (a) fast — phosphorylation increased by 2minutes and fell by 30minutes, (b) slow — phosphorylation continued to increase to 30minutes and (c) none — little change was observed or irradiated samples fell below controls. Total dose values were normalized to exam time for an averaged dose-rate in dose/sec for each exam. Relationships between patient biological responses and patient and exam parameters were investigated. Results: A clearer dose response at 30minutes is observed for young patients (<61yoa; R2>0.5) compared to old patients (>61yoa; R2<0.11). Fast responding patients were significantly younger than slow responding patients (p<0.05). Unlike in vivo samples, age did not significantly affect the patient response ex vivo. Additionally, fast responding patients received exams with significantly smaller dose-rate than slow responding patients (p<0.05). Conclusion: Age is a significant factor in the biological response suggesting that DDR may be more rapid in a younger population and slower as the population ages. Lack of an agerelated response ex vivo suggests a systemic response to radiation not present when irradiated outside the body. Dose-rate affects the biological response suggesting that patient response may be related to scan timing and dose delivery within an exam protocol. All authors receive(d) funding from a Master Research Agreement from Siemens Healthcare with UCLA Radiological Sciences.