Individual Variation Research Articles

Utilizing red blood cell distribution width (RDW) as a reliable biomarker to predict treatment effects after chimeric antigen receptor T cell therapy.

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker. After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3+ cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance. Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R2 = 0.76, p = 0.02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3.46, P = 0.03). Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.

Digital Subtraction Angiography of Cerebral Arteries: Influence of Cranial Dimensions on X-ray Tube Performance

(1) Background. Digital subtraction angiography (DSA) is indispensable for diagnosing cerebral aneurysms due to its superior imaging precision. However, optimizing X-ray parameters is crucial for accurate diagnosis, with X-ray tube settings significantly influencing image quality. Understanding the relationship between skull dimensions and X-ray parameters is pivotal for tailoring imaging protocols to individual patients. (2) Methods. A retrospective analysis of DSA data from a single center was conducted, involving 251 patients. Cephalometric measurements and statistical analyses were performed to assess correlations between skull dimensions and X-ray tube parameters (voltage and current). (3) Results. The study revealed significant correlations between skull dimensions and X-ray tube parameters, highlighting the importance of considering individual anatomical variations. Gender-based differences in X-ray parameters were observed, emphasizing the need for personalized imaging protocols. (4) Conclusions. Personalized approaches to DSA imaging, integrating individual anatomical variations and gender-specific differences, are essential for optimizing diagnostic outcomes. While this study provides valuable insights, further research across multiple centers and diverse imaging equipment is warranted to validate these findings.

Scale effects and implications of the stochastic structure of customer water demands

ABSTRACT The effect of different temporal (from seconds to months) and spatial aggregation scales (from individual users to full urban areas) on water demand behavior has been explored to a limited degree. The effort described here extends those works by evaluating the scale effects of residential water consumption in a unique US data set that covers 10,000 households with a 1-gallon (3.79 L) hourly resolution over 2 years. A preliminary data analysis and a sequential Principal Component Analysis (PCA) is carried out to assess the effect of different temporal (weekly, daily, hourly) and spatial aggregation (individual meters and groups every 10, 100 and 1,000 m) levels on demand. Results show that individual users act very differently from each other, and individual consumer variability is only canceled out when a significant number of households are aggregated. The implications of this finding are assessed from a hydraulic modeling perspective as the spatiotemporal scale of measurements may condition the type of analysis that can be carried out in practice. However, additional work is needed to explore the point at which it may be worth to embrace a micro (per fixture/household) or a macro (per node/network) approach for different purposes.

Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer-Cyclin-Dependent Kinase 4 and 6 Inhibitors: ASCO Guideline Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

The relative effects of direct and indirect written corrective feedback on L2 learning: The moderating role of field dependence/independence

The current study investigated the relative effects of direct and indirect written corrective feedback (WCF) on the learning of regular past tense, and the extent to which learning outcomes were related to individual variation in field dependence/independence (FDI). Fifty-nine Chinese intermediate second language (L2) learners of English were randomly assigned to two treatment groups and a control group. The two treatment groups carried out three written dictogloss tasks and received direct WCF and indirect WCF, respectively, on their erroneous use of regular past tense. The control group performed the same writing tasks but received feedback on the content of their writing. To evaluate the effect of treatment, a grammaticality judgement task and a picture description task were administered as the pretest, immediate posttest, and delayed posttest. The Group Embedded Figures Test was used to measure learners’ FDI orientation. The results showed that both treatment groups outperformed the control group on the posttests, but no significant differences were observed between the two treatment groups. In addition, the results suggested that FDI was related to learning outcomes as measured by the picture description task. Field independent learners had an overall advantage over field dependent learners, especially where indirect WCF was provided.

Sports integrities: a conceptual and methodological framework for analysis and policymaking

ABSTRACT Since the manipulation of sport competitions became one of the main threats to sport integrity, both the academy and international organizations have sought to establish a coherent conceptual framework that defines what criteria determine a manipulation and what are the factors that might cause it. Although the literature has shown that the manipulation of sport competition is a multifaceted phenomenon that includes individual, relational, organizational and institutional variables, most of the authors have focused their explanations on individual factors, and institutional prevention campaigns continue to understand match-fixing as a problem of moral failure of on-field sports actors. This work proposes a novel dynamic framework for analysis based on the theoretical roots on Morin’s paradigm of complexity and Archer’s critical realism. In addition to articulating the micro, meso, and macro factors together, the paper defends the idea of three conceptions of integrity, personal, competition and institutional, often operating simultaneously in the same space. Each one of these integrities, operates across individual, organizational and structural levels, acting recursively on the others, generating the gears of the global sports integrity. We then discuss the reasons, structures, opportunities and incentives that each of these integrities creates and fuels. We argue that the errors and ineffectiveness of the fight against the manipulation of sport competitions are largely due to a lack of understanding of, and appreciation for, the different conceptions of integrity and their interactions that require different approaches and differentiated public policies. We conclude with innovative possibilities for more effective policy-making processes in this space.

Within population plastic responses to combined thermal-nutritional stress differ from those in response to single stressors, and are genetically independent across traits in both males and females.

Phenotypic plasticity helps animals to buffer the effects of increasing thermal and nutritional stress created by climate change. Plastic responses to single and combined stressors can vary among genetically diverged populations. However, less is known about how plasticity in response to combined stress varies among individuals within a population or whether such variation changes across life-history traits. This is important because individual variation within populations shapes population-level responses to environmental change. Here, we used isogenic lines of Drosophila melanogaster to assess plasticity of egg-to-adult viability and sex-specific body size for combinations of two temperatures (25°C or 28°C) and three diets (standard diet, low caloric diet, or low protein:carbohydrate ratio diet). Our results reveal substantial within-population genetic variation in plasticity for egg-to-adult viability and wing size in response to combined thermal-nutritional stress. This genetic variation in plasticity was a result of cross-environment genetic correlations that were often < 1 for both traits, as well as changes in the expression of genetic variation across environments for egg-to-adult viability. Cross-sex genetic correlations for body size were weaker when the sexes were reared in different conditions, suggesting that the genetic basis of traits may change with the environment. Further, our results suggest that plasticity in egg-to-adult viability is genetically independent from plasticity in body size. Importantly, plasticity in response to diet and temperature individually differed from plastic shifts in response to diet and temperature in combination. By quantifying plasticity and the expression of genetic variance in response to combined stress across traits, our study reveals the complexity of animal responses to environmental change, and the need for a more nuanced understanding of the potential for populations to adapt to ongoing climate change.

Separating individual and group-level cooperation in the public goods game

Abstract Cooperation in the Public Goods Game (PGG) is determined by a mixture of individual differences (e.g., personality, social preferences) and group dynamics (e.g., reciprocation, social norms). However, to our knowledge, no thorough attempt has been made to separate individual and group levels of cooperation and quantify the variance in cooperation that can be attributed to the group level. In an analysis of ten open datasets (total N = 4,556, 1003 groups, 7–50 rounds), we chart the trajectory of individual and group-level variance across rounds of repeated PGGs. We find that the portion of group-level variance increases initially and plateaus around the fifth round, typically at a level between 20% and 50%. In addition, we identify four factors that increase the portion of group-level variance: (1) punishment opportunities; (2) detailed feedback including all group members’ decisions; (3) small groups (≤4 players); and (4) groups with homogenous social preferences.

Impact of the Double-Reduction Policy on Middle School Students Study

This study explores the impact of the Double-Reduction Policy on middle school students' study habits, academic performance, and overall wellbeing. The policy aims to reduce academic stress by decreasing homework load and classroom hours. Through this research, we examine the diverse effects that this policy has on students' perceptions and experiences. The majority of students see the policy favourably; they report lower levels of stress, better sleep habits, and more free time for extracurricular activities. However, concerns about a perceived lack of readiness for future academic activities as well as a decreased academic challenge and falling enthusiasm are voiced, especially among high achievers. With an emphasis on the function of observational learning, self-efficacy beliefs, modeling actions, and the dynamic interaction of personal and environmental elements, social cognitive theory provides a theoretical framework to comprehend the observed behaviors and results. This research highlights the necessity for balanced policies that promote well-being while retaining academic rigor as well as the need of taking into account individual variances in students' reactions to policy changes. These findings hold significant implications for teachers and policymakers. It highlights the need of educational policy that takes into account the varied life experiences of students in order to improve their health and success in school. More study is required to figure out how these policies will play out in the long run and what elements will have the most impact on individual outlooks and experiences.

Impact of distinct cognitive domains on gait variability in individuals with mild cognitive impairment and dementia.

Gait variability is a common feature in neurodegenerative diseases and has been linked to cognitive impairment. Despite this link, the influence of specific cognitive domains, such as memory, visual spatial skills, executive function, and verbal function on gait variability is not well-understood. To investigate the predictive value of these specific cognitive domains on gait variability in people with mild cognitive impairment (MCI) and dementia during preferred and dual task walking. One hundred and two participants with either MCI or dementia underwent a comprehensive cognitive assessment and completed preferred and dual-task walking trials on a pressure-sensing walkway. Gait variability was assessed using the PKMAS software. Lower extremity function was evaluated with a self-reported validated scale. Our findings indicate that only visual spatial abilities had a moderate predictive value on gait variability [F (1, 78) = 17.30, p < 0.01, r = 0.43], both in preferred pace walking (70% direct effect) and dual-task walking (90% direct effect) (p's < 0.05). Additionally, lower extremity functional skills had a significant indirect effect (30%) on gait variability in preferred walking contexts. For individuals diagnosed with MCI or dementia, increased gait variability may be driven by deficits in visual spatial processing. An increased understanding of the role of visual spatial processing in gait variability can aid in the assessment and management of individuals with MCI or dementia, potentially leading to targeted interventions to improve mobility and safety.

The modulatory effect of Al-Assi river trout fish meal on OCD manifestations and molecular mechanisms in BALB/c Mice

Background: Obsessive-Compulsive Disorder (OCD) is a type of anxiety disorder that is marked by intrusive and distressing thoughts, as well as repetitive behaviors. Trout fish (Oncorhynchus mykiss) is a functional food that might have potential therapeutic effects on many neurological disorders including OCD. Objective: This study aims to explore the effects of Al-Assi River trout fish meal, a dietary source of tryptophan, on obsessive-compulsive disorder (OCD) symptoms and related molecular pathways in BALB/c mice. Methods: OCD mice were divided into five groups: one control group without any treatment, one group treated with fluoxetine (a selective serotonin reuptake inhibitor), and three groups fed with different doses of trout fish meal (0, 7.5, and 15 g/kg body weight). The mice were subjected to various behavioral tests, such as the marble test, tail suspension test, sucrose preference test, and forced swim test, to evaluate OCD and depressive-like behaviors. Moreover, the expression and protein levels of genes involved in the serotonergic and GABAergic systems were measured. Results: The results indicated that trout fish meal had dose-dependent effects on OCD-like behaviors, revealing exacerbation at lower doses and improvement at higher doses. For instance, in the marble test, OCD mice fed with 7.5 g of trout fish/kg body weight buried more marbles than those fed with 15 g/kg of trout fish (4.5 vs 3.33 out of 6, p&gt;0.05). In the tail suspension test, the immobility time of OCD mice treated with fluoxetine was numerically lower than that of the untreated OCD mice (63.6 vs 87.3 seconds, p&gt;0.05). Furthermore, normal mice had different baseline gene expression profiles than OCD mice. Normal mice had the highest fold increase of Gabra gene expression (3.75) compared to the untreated OCD group, followed by groups treated with 7.5 and 15 g of trout fish/kg body weight (2.02 and 1.44, respectively). Conclusions: This study suggests that dietary interventions rich in tryptophan, such as trout fish meal, may have modulatory effects on OCD symptoms and molecular mechanisms in mice. However, the optimal dosing and individual variability need to be considered. More research is required to clarify the underlying mechanisms and to evaluate the potential efficacy of trout fish meal in treating OCD in humans. Keywords: BALB/c mice, OCD, qPCR, Western blotting, Gabra, Serotonin, Trout fish, Tryptophan.

A longitudinal evaluation of personalized intrinsic network topography and cognitive decline in Parkinson's disease.

Resting state functional magnetic resonance imaging (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network-based statistics (NBS) and calculations of mean inter- and intra-network connectivity within pre-defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow-up) increased intra-network connectivity, whereas decliners showed exclusively reduced intra-network and inter- (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter-network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra-network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter-network synchrony may support cognitive function in the face of PD-related network disruptions.

Leveraging individual differences in cue-reward learning to investigate the psychological and neural basis of shared psychiatric symptomatology: The sign-tracker/goal-tracker model.

In our modern environment, we are bombarded with stimuli or cues that exert significant influence over our actions. The extent to which such cues attain control over or disrupt goal-directed behavior is dependent on several factors, including one's inherent tendencies. Using a rodent model, we have shown that individuals vary in the value they place on stimuli associated with reward. Some individuals, termed "goal-trackers," primarily attribute predictive value to reward cues, whereas others, termed "sign-trackers," attribute predictive and incentive value. Thus, for sign-trackers, the reward cue is transformed into an incentive stimulus that is capable of eliciting maladaptive behaviors. The sign-tracker/goal-tracker animal model has allowed us to refine our understanding of behavioral and computational theories related to reward learning and to parse the underlying neural processes. Further, the neurobehavioral profile of sign-trackers is relevant to several psychiatric disorders, including substance use disorder, impulse control disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and posttraumatic stress disorder. This model, therefore, can advance our understanding of the psychological and neurobiological mechanisms that contribute to individual differences in vulnerability to psychopathology. Notably, initial attempts at translation-capturing individual variability in the propensity to sign-track in humans-have been promising and in line with what we have learned from the animal model. In this review, we highlight the pivotal role played by the sign-tracker/goal-tracker animal model in enriching our understanding of the psychological and neural basis of motivated behavior and psychiatric symptomatology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pre- and postsynaptic signatures in the prelimbic cortex associated with "alcohol use disorder" in the rat.

The transition to alcohol use disorder (AUD) involves persistent neuroadaptations in executive control functions primarily regulated by the medial prefrontal cortex. However, the neurophysiological correlates to behavioral manifestations of AUD are not fully defined. The association between cortical neuroadaptations and behavioral manifestations of addiction was studied using a multi-symptomatic operant model based on the DSM-5 diagnostic criteria for AUD. This model aimed to characterize an AUD-vulnerable and AUD-resistant subpopulation of outbred male Wistar rats and was combined with electrophysiological measurements in the prelimbic cortex (PL). Mirroring clinical observations, rats exhibited individual variability in their vulnerability to develop AUD-like behavior, including motivation to seek for alcohol (crit 1), increased effort to obtain the substance (crit 2), and continued drinking despite negative consequences (crit 3). Only a small subset of rats met all the aforementioned AUD criteria (3 crit, AUD-vulnerable), while a larger fraction was considered AUD-resilient (0 crit). The development of AUD-like behavior was characterized by disruptions in glutamatergic synaptic activity, involving decreased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and heightened intrinsic excitability in layers 2/3 PL pyramidal neurons. These alterations were concomitant with a significant impairment in the ability of mGlu2/3 receptors to negatively regulate glutamate release in the PL but not in downstream regions like the basolateral amygdala or nucleus accumbens core. In conclusion alterations in PL synaptic activity were strongly associated with individual addiction scores, indicating their role as potential markers of the behavioral manifestations linked to AUD psychopathology.

Raman hyperspectroscopy of saliva and machine learning for Sjögren’s disease diagnostics

Sjögren's disease is an autoimmune disorder affecting exocrine glands, causing dry eyes and mouth and other morbidities. Polypharmacy or a history of radiation to the head and neck can also lead to dry mouth. Sjogren's disease is often underdiagnosed due to its non-specific symptoms, limited awareness among healthcare professionals, and the complexity of diagnostic criteria, limiting the ability to provide therapy early. Current diagnostic methods suffer from limitations including the variation in individuals, the absence of a single diagnostic marker, and the low sensitivity and specificity, high cost, complexity, and invasiveness of current procedures. Here we utilized Raman hyperspectroscopy combined with machine learning to develop a novel screening test for Sjögren's disease. The method effectively distinguished Sjögren's disease patients from healthy controls and radiation patients. This technique shows potential for development of a single non-invasive, efficient, rapid, and inexpensive medical screening test for Sjögren's disease using a Raman hyper-spectral signature.

Statistical process monitoring creates a hemodynamic trajectory map after pediatric cardiac surgery: A case study of the arterial switch operation

AbstractPostoperative critical care management of congenital heart disease patients requires prompt intervention when the patient deviates significantly from clinician‐determined vital sign and hemodynamic goals. Current monitoring systems only allow for static thresholds to be set on individual variables, despite the expectations that these signals change as the patient recovers and that variables interact. To address this incongruency, we have employed statistical process monitoring (SPM) techniques originally developed to monitor batch industrial processes to monitor high‐frequency vital sign and hemodynamic data to establish multivariate trajectory maps for patients with d‐transposition of the great arteries following the arterial switch operation. In addition to providing multivariate trajectory maps, the multivariate control charts produced by the SPM framework allow for assessment of adherence to the desired trajectory at each time point as the data is collected. Control charts based on slow feature analysis were compared with those based on principal component analysis. Alarms generated by the multivariate control charts are discussed in the context of the available clinical documentation.

Examining Adolescent Language Performance in Discourse Production Across Four Elicitation Tasks.

Comprehensive spoken language assessment should include the evaluation of language use in naturalistic contexts. Discourse elicitation and analysis provides the opportunity for such an evaluation to occur. In this article, our overall aim was to describe adolescents' language performance on four elicitation tasks and determine if there are task-related differences across the elicitation tasks. Forty-four typically developing adolescents with ages ranging from 12;2 to 17;11 (years;months; M = 15;2; 21 boys and 23 girls) participated in the study. They completed four spoken discourse tasks: (a) story generation using a wordless picture book, (b) fable retell, (c) six personal narratives in response to emotion-based prompts, and (d) monologic response to two stories that contained a moral dilemma. Responses were transcribed and analyzed for four language performance measures tapping into language productivity, syntactic complexity, lexical diversity, and verbal facility. Despite individual variability in performance, mean scores were close to median scores for most measures, suggesting a symmetrical distribution. As expected, all four language performance measures were significantly different across the four elicitation tasks. The personal narrative task elicited the longest samples, with the highest verbal fluency. In contrast, both lexical diversity and syntactic complexity were the strongest in response to the fable retell and the moral dilemma tasks. This investigation provides speech-language pathologists with an overview of how task-related factors may impact adolescent language performance. These findings may be used to support their clinical decision-making processes in choosing a suitable discourse task when conducting a comprehensive spoken language assessment. Three hypothetical case examples are used to illustrate the decision-making process. https://doi.org/10.23641/asha.25761768.

Biopharmaceutical distribution and pharmacodynamic evaluation of intra nasal in-situ gel of Lamotrigine for brain targeted drug delivery

Background: The present research investigates the nasal delivery of Lamotrigine by incorporating it into a natural in-situ gelling system. Additionally, the retention of the drug in the nasal cavity was enhanced by employing the natural mucoadhesive polymer locust bean gum (LBG). A preliminary investigation was conducted to determine the optimal concentration of gellan gum. The dosage of the drug was calculated using the Robinson Erikson equation. The central composite design was utilized to optimize the influence of individual variables such as gellan gum and locust bean gum on various responses, including gelation time, gel viscosity, mucoadhesive strength, and the time taken for the drug to release half of its initial concentration (t50). The goal of the current study was to evaluate the in-vivo effectiveness of intra nasal in-situ gel of Lamotrigine. Methodology: The pharmacokinetic and tissue distribution studies were carried out to evaluate the brain targeting efficiency of lamotrigine. Blood samples and tissues of various vital organs like brain, liver, kidneys and heart were obtained at different time intervals, plasma and tissue concentration of Lamotrigine was estimated by reverse phase HPLC. Results: According to the pharmacokinetic analysis, Cmax and AUC0-α is found to be significantly more (P&lt;0.05) for nasal route compared to oral route. In comparison to the oral route, Cmax and AUC0-α was 7 and 6.5 folds more for IN route. The absolute bioavailability was found to be 159.07%. with regard to the oral group, minimal drug was present in any of the other tissue samples. In the pharmacodynamic data also the formulation through nasal route showed a significant difference compared to oral route (pure drug suspension) delivery in PTZ induced study. Keywords: Lamotrigine, in-vivo study, tissue distribution, pharmacodynamics

In vitro evaluation of novel SN-38 prodrug activated by α-rhamnosidase of exogenous enzyme.

This study introduces the α-rhamnose (Rham)-conjugated prodrug of SN-38 (Rham-SN-38) as a promising alternative to irinotecan. α-rhamnosidase, responsible for SN-38 release from Rham-SN-38, does not express in human cells, minimizing individual variability and side effects. The injection of the α-rhamnosidase into the tumor tissues makes it possible, for the first time, to activate the Rham-SN-38. Furthermore, α-rhamnosidase demonstrates significantly higher activity than carboxylesterase, the specific enzyme activating irinotecan. SN-38 release mediated by α-rhamnosidase completes within 2h, with a kcat/Km value approximately 5.0 × 104-fold higher than that of irinotecan. The 50% inhibition concentration (IC50) of Rham-SN-38 against three types of cancer cells and one normal cell exceeds 4.5 × 103nM. The addition of α-rhamnosidase significantly increases cytotoxicity, with IC50 comparable to free SN-38. The QIC50, an index reflecting the difference in cytotoxicity with and without α-rhamnosidase, exceeds approximately 1.0 × 102-fold. Rham-SN-38, synthesized in this study, demonstrates significant potential as a prodrug for cancer therapy.

Bidirectional relationship between attentional deficits and escalation of nicotine intake in male rats.

People with tobacco addiction have deficits in cognition, in particular deficits in attention. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance. Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration. We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits.