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PubMed2006

Transient and steady-state dynamics of cortical adaptation.

Adaptation is a ubiquitous property of all sensory pathways of the brain and thus likely critical in the encoding of behaviorally relevant sensory information. Despite evidence identifying specific biophysical mechanisms contributing to sensory adaptation, its functional role in sensory encoding is not well understood, particularly in the natural environment where transient rather than steady-state activity could dominate the neuronal representation. Here, we show that the heterogeneous transient and steady-state adaptation dynamics of single cortical neurons in the rat vibrissa system were well characterized by an underlying state variable. The state was directly predictable from temporal response properties that capture the time course of postexcitatory suppression following an isolated vibrissa deflection. Altering the initial state, by preceding the periodic stimulus with an additional vibrissa deflection, strongly influenced single-cell transient cortical adaptation responses. Despite the different transient activity, neurons reached the same steady-state adapted response with a time to steady state that was independent of the initial state. However, the differences in transient activity observed on small time scales were not present when activity was integrated over the longer time scale of a stimulus cycle. Taken together, the results here demonstrate that although adaptation can have significant effects on transient neuronal activity and direction selectivity, a simple measure of the time course of suppression following an isolated stimulus predicted a large portion of the observed adaptation dynamics.

Action Potentials↗

PubMed2004

Cognitive transformation as a marker of resilience.

Individuals often report positive, transformative changes in response to adversity. Cognitive transformation involves a turning point in a person's life characterized by: (1) the recognition that coping with adversity resulted in new opportunities; and, (2) the reevaluation of the experience from one that was primarily traumatic or threatening to one that is growth-promoting. Cognitive transformation often signifies enhanced adaptation to adverse circumstances, and thus, is a marker of resilience. The present study examined the relationship of cognitive transformation to indicators of resilience among 35 acutely bereaved young adults and a nonbereaved comparison group. Findings strongly supported the hypothesis that transformation predicts resilience, and may reduce one's risk trajectory to enhance adaptation. Results are discussed in terms of their implications for research on resilience, and on recovery from acute or chronic adverse circumstances, including addiction.

Adaptation, Psychological↗

PubMed1993

The locus coeruleus as a site for integrating corticotropin-releasing factor and noradrenergic mediation of stress responses.

Anatomic and electrophysiologic studies have provided evidence that CRF meets some of the criteria as a neurotransmitter in the noradrenergic nucleus, the locus coeruleus (LC), although some of the criteria have yet to be satisfied. Thus, immunohistochemical findings suggest that CRF innervates the LC, but this must be confirmed at the ultrastructural level. CRF alters discharge activity of LC neurons and these effects are mimicked by some stressors. Moreover, the effects of hemodynamic stress on LC activity are prevented by a CRF antagonist. However, it has not been demonstrated that stimulation of CRF neurons that project to the LC activates the LC or that the effects of such stimulation are prevented by a CRF antagonist. The role of CRF in LC activation by stressors other than hemodynamic stress needs to be determined. It could be predicted that the effects of CRF neurotransmission in the LC during stress would enhance information processing concerning the stressor or stimuli related to the stressor by LC target neurons. One consequence of this appears to be increased arousal. Although this may be adaptive in the response to an acute challenge, it could be predicted that chronic CRF release in the LC would result in persistently elevated LC discharge and norepinephrine release in targets. This could be associated with hyperarousal and loss of selective attention as occurs in certain psychiatric diseases. Manipulation of endogenous CRF systems may be a novel way in which to treat psychiatric diseases characterized by these maladaptive effects.

Animals↗

PubMed2005

Machine learning can improve prediction of severity in acute pancreatitis using admission values of APACHE II score and C-reactive protein.

BACKGROUND: Acute pancreatitis (AP) has a variable course. Accurate early prediction of severity is essential to direct clinical care. Current assessment tools are inaccurate, and unable to adapt to new parameters. None of the current systems uses C-reactive protein (CRP). Modern machine-learning tools can address these issues. METHODS: 370 patients admitted with AP in a 5-year period were retrospectively assessed; after exclusions, 265 patients were studied. First recorded values for physical examination and blood tests, aetiology, severity and complications were recorded. A kernel logistic regression model was used to remove redundant features, and identify the relationships between relevant features and outcome. Bootstrapping was used to make the best use of data and obtain confidence estimates on the parameters of the model. RESULTS: A model containing 8 variables (age, CRP, respiratory rate, pO2 on air, arterial pH, serum creatinine, white cell count and GCS) predicted a severe attack with an area under the receiver-operating characteristic curve (AUC) of 0.82 (SD 0.01). The optimum cut-off value for predicting severity gave sensitivity and specificity of 0.87 and 0.71 respectively. The predictions were significantly better (p = 0.0036) than admission APACHE II scores in the same patients (AUC 0.74) and better than historical admission APACHE II data (AUC 0.68-0.75). CONCLUSIONS: This system for the first time combines admission values of selected components of APACHE II and CRP for prediction of severe AP. The score is simple to use, and is more accurate than admission APACHE II alone. It is adaptable and would allow incorporation of new predictive factors.

APACHE↗

PubMed1997

Altered astronaut lower limb and mass center kinematics in downward jumping following space flight.

Astronauts exposed to the microgravity conditions encountered during space flight exhibit postural and gait instabilities upon return to earth that could impair critical postflight performance. The aim of the present study was to determine the effects of microgravity exposure on astronauts' performance of two-footed jump landings. Nine astronauts from several Space Shuttle missions were tested both preflight and postflight with a series of voluntary, two-footed downward hops from a 30-cm-high step. A video-based, three-dimensional motion-analysis system permitted calculation of body segment positions and joint angular displacements. Phase-plane plots of knee, hip, and ankle angular velocities compared with the corresponding joint angles were used to describe the lower limb kinematics during jump landings. The position of the whole-body center of mass (COM) was also estimated in the sagittal plane using an eight-segment body model. Four of nine subjects exhibited expanded phase-plane portraits postflight, with significant increases in peak joint flexion angles and flexion rates following space flight. In contrast, two subjects showed significant contractions of their phase-plane portraits postflight and three subjects showed insignificant overall changes after space flight. Analysis of the vertical COM motion generally supported the joint angle results. Subjects with expanded joint angle phase-plane portraits postflight exhibited larger downward deviations of the COM and longer times from impact to peak deflection, as well as lower upward recovery velocities. Subjects with postflight joint angle phase-plane contraction demonstrated opposite effects in the COM motion. The joint kinematics results indicated the existence of two contrasting response modes due to microgravity exposure. Most subjects exhibited "compliant" impact absorption postflight, consistent with decreased limb stiffness and damping, and a reduction in the bandwidth of the postural control system. Fewer subjects showed "stiff" behavior after space flight, where contractions in the phase-plane portraits pointed to an increase in control bandwidth. The changes appeared to result from adaptive modifications in the control of lower limb impedance. A simple 2nd-order model of the vertical COM motion indicated that changes in the effective vertical stiffness of the legs can predict key features of the postflight performance. Compliant responses may reflect inflight adaptation due to altered demands on the postural control system in microgravity, while stiff behavior may result from overcompensation postflight for the presumed reduction in limb stiffness inflight.

Acceleration↗

PubMed1998

Adaptation in a rotating artificial gravity environment.

The centripetal force generated by a rotating space vehicle is a potential source of artificial gravity. Minimizing the cost of such a vehicle dictates using the smallest radius and highest rotation rate possible, but head movements made at high rotation rates generate disorienting, nauseogenic cross-coupled semicircular canal stimulation. Early studies suggested 3 or 4 rpm as the highest rate at which humans could adapt to this vestibular stimulus. These studies neglected the concomitant Coriolis force actions on the head/neck system. We assessed non-vestibular Coriolis effects by measuring arm and leg movements made in the center of a rotating room turning at 10 rpm and found that movement endpoints and trajectories are initially deviated; however, subjects readily adapt with 10-20 additional movements, even without seeing their errors. Equilibrium point theories of motor control errantly predict that Coriolis forces will not cause movement endpoint errors so that subjects will not have to adapt their reaching movements during rotation. Adaptation of movement trajectory acquired during Coriolis force perturbations of one arm transfers to the unexposed arm but there is no intermanual transfer of endpoint adaptation indicating that neuromotor representations of movement endpoint and trajectory are separable and can adapt independently, also contradictory to equilibrium point theories. Touching a surface at the end of reaching movements is required for complete endpoint adaptation in darkness but trajectory adapts completely with or without terminal contact. We have also made the first kinematic measurements of unconstrained head movements during rotation, these movements show rapid adaptation to Coriolis force perturbations. Our results point to methods for achieving full compensation for rotation up to 10 rpm.

Adaptation, Physiological↗

PubMed1994

Ionizing radiation and genetic risks. V. Multifactorial diseases: a review of epidemiological and genetic aspects of congenital abnormalities in man and of models on maintenance of quantitative traits in populations.

This paper discusses (a) data on the epidemiological and etiological aspects of human congenital abnormalities, (b) the multifactorial threshold model and other models which have been proposed to explain their inheritance patterns and recurrence risks in families and (c) current concepts on mechanisms on the prevalence of heritable variation for quantitative traits in populations. Congenital abnormalities, which afflict an estimated 6% of all live births, are etiologically heterogeneous. The majority of these do not follow Mendelian transmission patterns, but do 'run' in families. The multifactorial threshold model is an extension of genetic principles developed for quantitative traits to all-or-none traits; in its simplest formulation, it assumes the existence in the population of an underlying normally distributed 'liability' (which is due to numerous genetic and environmental factors acting additively, each contributing a small amount of liability) and of a 'threshold' beyond which the individual is affected. For most congenital abnormalities, the nature of these factors remains unknown. Other models assume fewer causal factors although, again, these remain to be identified. The question of how considerable heritable variation for most quantitative/polygenic traits has come to exist is a long-standing one in evolutionary population genetics. Models postulating that its existence is consistent with a balance between recurrent mutation and stabilizing selection or suggesting the possible operation of other mechanisms have been published in the literature. In the absence of knowledge on mechanisms responsible for the stable prevalences of congenital abnormalities or other multifactorial conditions in the population (but which is required to predict the consequences of an increase in mutation rate on their prevalences) it is necessary (a) to adapt and use concepts derived from quantitative and evolutionary population genetics and (b) to examine how sensitive the predictions are to the assumptions used, and how consistent they are with biological realities.

Abnormalities, Radiation-Induced↗

PubMed1994

Biofilm accumulation model that predicts antibiotic resistance of Pseudomonas aeruginosa biofilms.

A computer model of biofilm dynamics was adapted to incorporate the activity of an antimicrobial agent on bacterial biofilm. The model was used to evaluate the plausibility of two mechanisms of biofilm antibiotic resistance by qualitative comparison with data from a well-characterized experimental system (H. Anwar, J. L. Strap, and J. W. Costerton, Antimicrob. Agents Chemother. 36:1208-1214, 1992). The two mechanisms involved either depletion of the antibiotic by reaction with biomass or physiological resistance due to reduced bacterial growth rates in the biofilm. Both mechanisms predicted the experimentally observed resistance of 7-day-old Pseudomonas aeruginosa biofilms compared with that of 2-day-old ones. A version of the model that incorporated growth rate-dependent killing predicted reduced susceptibility of thicker biofilms because oxygen was exhausted within these biofilms, leading to very slow growth in part of the biofilm. A version of the model that incorporated a destructive reaction of the antibiotic with biomass likewise accounted for the relative resistance of thicker biofilms. Resistance in this latter case was due to depletion of the antibiotic in the bulk fluid rather than development of a gradient in the antibiotic concentration within the biofilm. The modeling results predicted differences between the two cases, such as in the survival profiles within the biofilm, that could permit these resistance mechanisms to be experimentally distinguished.

Anti-Bacterial Agents↗

PubMed1998

Cross-cultural adaptation and validation of an Argentine Spanish Version of the Stanford Childhood Health Assessment Questionnaire.

OBJECTIVES: To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). METHODS: Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. RESULTS: The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children > 10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent-patient) were highly correlated (r = 0.986). CONCLUSIONS: Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.

Activities of Daily Living↗

PubMed2001

Endothelial nitric oxide synthase gene polymorphism and maternal vascular adaptation to pregnancy.

A common polymorphism of the endothelial NO synthase gene that predicts a Glu298Asp amino acid substitution in the mature protein has been associated with cardiovascular disorders in which NO bioactivity is impaired. However, the influence of this polymorphism on endothelial function is unknown. Healthy pregnancy is associated with enhanced endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery, a response mediated by NO. In this study, we investigated the effect of the endothelial NO synthase Glu298Asp polymorphism on endothelium-dependent vasodilation in early pregnancy, making the hypothesis that any genotype-dependent differences in NO generation would be more marked during pregnancy, when the production of NO is upregulated. FMD of the brachial artery was recorded during the first trimester in 139 healthy women with normal singleton pregnancies genotyped for the Glu298Asp variant of endothelial NO synthase. Maternal FMD exhibited a codominant inverse relation with the number of Asp298 alleles (r=-0.21, P=0.01). Among homozygotes for endothelial NO synthase Asp298, FMD (7.99+/-1.46%) was significantly lower than that observed among individuals homozygous for endothelial NO synthase Glu298 (10.12+/-3.44) (P=0.002). In a backward stepwise multiple regression analysis, vessel size (P<0.0001) and Glu298Asp polymorphism (P=0.01) were significantly and independently correlated with FMD. Our findings indicate that the endothelial NO synthase Glu298Asp polymorphism is associated with differences in endothelium-dependent dilation at 12-week gestation and are the first to implicate genetic factors in the normal vascular adaptation to pregnancy. They also provide a potential mechanism linking the endothelial NO synthase polymorphism with the development of cardiovascular disorders and have implications for understanding the genetic basis of preeclampsia.

Adaptation, Physiological↗

PubMed1998

Modulation of calcium-dependent postsynaptic depression contributes to an adaptive sensory filter.

Modulation of calcium-dependent postsynaptic depression contributes to an adaptive sensory filter. J. Neurophysiol. 80: 3352-3355, 1998. The ability of organisms to ignore unimportant patterns of sensory input may be as critical as the ability to attend to those that are behaviorally relevant. Mechanisms used to reject irrelevant inputs range from peripheral filters, which allow only restricted portions of the spectrum of possible inputs to pass, to higher-level processes, which actively select stimuli to be "attended to." Recent studies of several lower vertebrates demonstrate the presence of adaptive sensory filters, which "learn," with a time course of a few minutes, to cancel predictable patterns of sensory input without compromising responses to novel stimuli. Predictable stimuli include "reafferent" stimuli, which occur as a result of an animal's own activity, as well as stimuli that are simply repetitive. The adaptive characteristic of these filters depends on an anti-Hebbian form of synaptic plasticity that modulates the strength of multisensory dendritic inputs resulting in the genesis of "negative image" signals, which cancel the predicted pattern of sensory afference. This report provides evidence that the mechanism underlying the anti-Hebbian plasticity involves the modulation of a calcium-dependent form of postsynaptic depression.

Animals↗

PubMedDate not supplied

Orbital prefrontal cortex and guidance of instrumental behavior of rats by visuospatial stimuli predicting reward magnitude.

The orbital prefrontal cortex (OPFC) is part of a circuitry mediating the perception of reward and the initiation of adaptive behavioral responses. We investigated whether the OPFC is involved in guidance of the speed of instrumental behavior by visuospatial stimuli predictive of different reward magnitudes. Unoperated rats, sham-lesioned rats, and rats with bilateral lesions of the OPFC by N-methyl-D-aspartate (NMDA) were trained in a visuospatial discrimination task. The task required a lever press on the illuminated lever of two available to obtain a food reward. Different reward magnitudes were permanently assigned to lever presses to respective sides of the operant chamber; that is, responses to one lever (e.g., the left one) were always rewarded with one pellet and responses to the other lever with five pellets. On each trial, the position of the illuminated lever was pseudorandomly determined in advance. Results revealed that OPFC lesions did not impair acquisition of the task, as the speed of conditioned responses was significantly shorter with expectancy of a high reward magnitude. In addition, during reversal, shift and reshift of lever position-reward magnitude contingencies and under extinction conditions, performance of the OPFC-lesioned and control groups did not differ. It is concluded that the OPFC in rats might not be critical for adapting behavioral responses to changes of stimulus-reward magnitude contingencies signaled by visuospatial cues.

Animals↗

PubMed2006

ADAAPT: Amgen's data access, analysis, and prediction tools.

The Amgen's Data Access Analysis Prediction Tools (ADAAPT) system is a desktop decision support tool developed to provide flexible access and analysis of chemical and biological data. The system is platform independent, adaptable, easily deployed, and scalable. It consists of four main modules: access, analysis, prediction, and tools. The access module contains numerous user interfaces designed to retrieve data easily. The analysis module provides standard computational tools to perform property calculation, QSAR/QSPR, and statistical analyses. The prediction module contains in-house models to calculate a drug-likeness score and absorption index. Finally, the tools module provides a wide array of features that are of general interest to our scientists.

Computer Systems↗

PubMed2001

Pathogen fitness penalty as a predictor of durability of disease resistance genes.

Host plant resistance has been used extensively for disease control in many crop species; however, the resistance conferred by many sources is not durable as a result of rapid changes in the pathogen. Although many resistance genes have been identified in plant germplasm, there is no easy way to predict the quality or durability of these resistance genes. In this review, we revisit the hypothesis that resistance genes imposing a high penalty to the pathogen for adaptation will likely be durable. By elucidating the molecular changes involved in pathogen adaptation and the associated fitness cost, a proactive approach may be developed to predict the durability of resistance genes available for deployment.

Bacteria↗

PubMed1997

Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B.

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.

Alanine Transaminase↗

PubMedDate not supplied

Toward a greater appreciation of noncovalent chemical/DNA interactions: application of biological and computational approaches.

Noncovalent DNA interactions, e.g., DNA intercalation and DNA groove-binding, have not been well studied relative to covalent interactions largely due to the inability of predicting and detecting such events in intact cells. We have adapted an in vitro bleomycin amplification method for DNA intercalation for use in cultured V79 Chinese hamster cells and have validated this approach through the use of a three-dimensional DNA computational docking model that quantifies potential strength of DNA intercalative binding based on electrostatics and hydrogen bonding. For many structural classes of molecules, DNA intercalation is necessary but not sufficient for genotoxicity. The present article reviews our progress to date in predicting and confirming noncovalent binding of drugs and other chemicals and in understanding the mechanistic relationship between intercalation and genotoxicity.

Animals↗

PubMed2026

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 ± 0.0994, with a Log-rank testp-value of 1.6553×10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 ± 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 ± 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 ± 0.1211) and discrete-time survival models such as DeepHit (0.7655 ± 0.1041) and Nnet-surv (0.7694 ± 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 ± 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 ± 0.0818) and Multimodal Co-Attention Transformer (0.8102 ± 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell↗

PubMed2002

Bayesian population model of methotrexate to guide dosage adjustments for folate rescue in patients with breast cancer.

BACKGROUND: Methotrexate (MTX) infusions may induce severe side-effects, and alkaline hydration along with folinic acid rescue is a common way to reduce such toxic risks. The purpose of this study was to develop an adaptive rescue strategy based upon the early detection of patients with impaired MTX elimination. METHODS AND RESULTS: In this study, we propose a simple population-based Bayesian approach for predicting MTX plasma concentration from a limited number of samples, so as to adapt both duration and dosage of the rescue agent to be used next. Ten kinetic profiles obtained after 10 courses of MTX (1.5 g/m2) in seven patients with inflammatory breast cancer were used to establish the population pharmacokinetic parameters (Cl, 8.16 L/h; t1/2, 12.7 h). This population was next involved in the Bayesian estimation of MTX individual pharmacokinetic parameters from only two blood samples (T24 and T36 h), thus allowing one to forecast the elimination of this drug by predicting MTX levels at 48 h. According to the MTX concentrations predicted during the elimination phase, folinic acid rescue was then prolonged in patients likely to be overexposed. CONCLUSION: The Bayesian estimation presented in this study was an easy and convenient method to efficiently detect patients with impaired MTX elimination in routine clinical practice. This information enabled the introduction of strategies for minimizing the risk of severe drug toxicity.

Adult↗