Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia.

OBJECTIVES: Achieving a major molecular response (MMR) is the goal of imatinib therapy for chronic myeloid leukemia. However, the association between gender, BCR-ABL transcript type, and age with MMR is not well understood and often controversial. METHODS: We retrospectively analyzed 166 patients who have been treated with imatinib for up to 10 yr. RESULTS: Men had a lower MMR rate than women (63.3% vs. 81.6%, P = 0.006) and a shorter time to relapse (median 354 vs. 675 d, P = 0.049), while patients with b3a2 or with both b3a2 and b2a2 break point transcripts had higher MMR rate than those with b2a2 (81.8%, 77.1% vs. 60.7%, P = 0.023 for b3a2 vs. b2a2, P = 0.043 for both vs. b2a2). A striking difference was found between men with b2a2 and women with both b2a2 and b3a2 in terms of MMR rate (43.8% vs. 88.9%), MMR rate within 6 months (7.1% vs. 62.5%) and the time to MMR (median d 493 vs. 159, P = 0.036). CONCLUSIONS: Both gender and BCR-ABL transcript, but not age, were significantly associated with the molecular response. Men with b2a2 represent a less favorable group in their response to imatinib treatment and may need alternative therapy regimen and closer monitoring.

Genetic Risk Evaluation in Wet Age-Related Macular Degeneration Treatment Response.

OBJECTIVE: To evaluate the pharmacogenetic relationship between CFH haplotypes and single nucleotide polymorphisms (SNPs) with response to ranibizumab treatment for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: This was a prospective cohort study involving 70 treatment-naive nAMD patients. Patients were genotyped for CFH haplotypes and SNPs in the C3, ARMS2, and mtDNA genes. Visual acuity and central macular thickness were assessed at baseline and during 6 monthly follow-up visits. Multivariate logistic regression was used to determine the association between genotypes and a gain of ≥15 letters at the 6-month endpoint after adjusting for potential confounders. RESULTS: CFH haplotypes were associated with a gain of ≥15 letters at the 6-month endpoint (p = 0.046). Patients expressing protective haplotypes were more likely to achieve a gain of ≥15 letters relative to the greatly increased risk haplotypes [OR 6.58 (95% CI: 1.37, 31.59)]. CONCLUSION: CFH is implicated in nAMD patient treatment response to ranibizumab.

Prevalence of NTRK Fusions in Canadian Solid Tumour Cancer Patients.

INTRODUCTION: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in ~ 0.3% of all solid tumours but are enriched in some rare tumour types. Tropomyosin receptor kinase (TRK) inhibitors larotrectinib and entrectinib are approved as tumour-agnostic therapies for solid tumours harbouring NTRK fusions. METHODS: This study investigated the prevalence of NTRK fusions in Canadian patients and also aimed to help guide NTRK testing paradigms through analysis of data reported from a national clinical diagnostic testing program between September 2019 and July 2021. RESULTS: Of 1,687 patients included in the final analysis, NTRK fusions were detected in 0.71% (n = 12) of patients representing salivary gland carcinoma (n = 3), soft tissue sarcoma (n = 3), CNS (n = 3), and one in each of melanoma, lung, and colorectal cancer. All three salivary gland carcinomas contained ETV6-NTRK3 fusions. Thirteen (0.77%) clinically actionable incidental findings were also detected. Two of the 13 samples containing incidental findings were NTRK fusion-positive (GFOD1-NTRK2, FGFR3-TACC3 in a glioblastoma and AFAP1-NTRK2, BRAF c.1799T>A in a glioma). The testing algorithm screened most patient samples via pan-TRK immunohistochemistry (IHC), whereas samples from the central nervous system (CNS), pathognomonic cancers, and confirmed/ putative NTRK fusion-positive samples identified under research protocols were reflexed straight to next-generation sequencing (NGS). CONCLUSION: These findings highlight the benefit and practicality of a diagnostic testing program to identify patients suitable for tumour-agnostic TRK inhibitor therapies, as well as other targeted therapies, due to clinically actionable incidental findings identified. Collectively, these findings may inform future guidance on selecting the appropriate testing approach per tumour type and on optimal NTRK testing algorithms.

Neural Mechanisms of Social and Nonsocial Reward Prediction Errors in Adolescents with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the neural mechanisms subsuming reward prediction errors in ASD are poorly understood. In the current study, we investigated neural responses during social and nonsocial reward prediction errors in 22 adolescents with ASD (ages 12-17) and 20 typically developing control adolescents (ages 12-18). Participants performed a reward prediction error task using both social (i.e., faces) and nonsocial (i.e., objects) rewards during a functional magnetic resonance imaging scan. Reward prediction errors were defined in two ways: (a) the signed prediction error, the difference between the experienced and expected reward; and (b) the thresholded unsigned prediction error, the difference between expected and unexpected outcomes regardless of magnitude. During social reward prediction errors, the ASD group demonstrated the following differences relative to the TD group: (a) signed prediction error: decreased activation in the right precentral gyrus and increased activation in the right frontal pole; and (b) thresholded unsigned prediction error: increased activation in the right anterior cingulate gyrus and bilateral precentral gyrus. Groups did not differ in brain activation during nonsocial reward prediction errors. Within the ASD group, exploratory analyses revealed that reaction times and social-communication impairments were related to precentral gyrus activation during social prediction errors. These findings elucidate the neural mechanisms of social reward prediction errors in ASD and suggest that ASD is characterized by greater neural atypicalities during social, relative to nonsocial, reward prediction errors in ASD. Autism Res 2020, 13: 715-728. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We used brain imaging to evaluate differences in brain activation in adolescents with autism while they performed tasks that involved learning about social and nonsocial information. We found no differences in brain responses during the nonsocial condition, but differences during the social condition of the learning task. This study provides evidence that autism may involve different patterns of brain activation when learning about social information.

Postal survey of physicians and laboratories: practices and perceptions of molecular oncology testing.

BACKGROUND: Molecular oncology testing (MOT) to detect genomic alterations underlying cancer holds promise for improved cancer care. Yet knowledge limitations regarding the delivery of testing services may constrain the translation of scientific advancements into effective health care. METHODS: We conducted a cross-sectional, self-administered, postal survey of active cancer physicians in Ontario, Canada (N = 611) likely to order MOT, and cancer laboratories (N = 99) likely to refer (i.e., referring laboratories) or conduct (i.e., testing laboratories) MOT in 2006, to assess respondents' perceptions of the importance and accessibility of MOT and their preparedness to provide it. RESULTS: 54% of physicians, 63% of testing laboratories and 60% of referring laboratories responded. Most perceived MOT to be important for treatment, diagnosis or prognosis now, and in 5 years (61% - 100%). Yet only 45% of physicians, 59% of testing labs and 53% of referring labs agreed that patients in their region were receiving MOT that is indicated as a standard of care. Physicians and laboratories perceived various barriers to providing MOT, including, among 70% of physicians, a lack of clear guidelines regarding clinical indications, and among laboratories, a lack of funding (73% - 100%). Testing laboratories were confident of their ability to determine whether and which MOT was indicated (77% and 82% respectively), and perceived that key elements of formal and continuing education were helpful (75% - 100%). By contrast, minorities of physicians were confident of their ability to assess whether and which MOT was indicated (46% and 34% respectively), and while majorities considered various continuing educational resources helpful (68% - 75%), only minorities considered key elements of formal education helpful in preparing for MOT (17% - 43%). CONCLUSION: Physicians and laboratory professionals were enthusiastic about the value of MOT for cancer care but most did not believe patients were gaining adequate access to clinically necessary testing. Further, our results suggest that many were ill equipped as individual stakeholders, or as a coordinated system of referral and interpretation, to provide MOT. These challenges should inspire educational, training and other interventions to ensure that developments in molecular oncology can result in optimal cancer care.

Discourse of 'transformational leadership' in infection control.

The article explores the impact of the ;transformational leadership' style in the role of modern matron with regards to infection control practices. Policy and guidance on the modern matron role suggest that it is distinctive in its combination of management and clinical components, and in its reliance on transformational leadership. Senior nurses are therefore expected to motivate staff by creating high expectations, modelling appropriate behaviour, and providing personal attention to followers by giving respect and responsibility. In this article, we draw on policy documents and interview data to explore the potential impact of this new management style on infection control practices. Combining the techniques of discourse analysis and corpus linguistics, we identify examples where matrons appear to disassociate themselves from the role of ;an empowered manager' who has control over human and financial resources to resolve problems in infection control efficiently.

The effects of rearing method on social behaviors of mentored, captive-reared juvenile California condors.

Puppet-reared and parent-reared captive-bred California condor (Gymnogyps californianus) juveniles were studied before their release into the wild. Behavioral data were collected during social interactions within two cohorts of juveniles (N = 11) and their adult mentors (N = 5). The purposes of this study were to (1) document the social behaviors of mentored juvenile California condors, and (2) compare social behaviors for two different rearing methods (puppet-reared versus parent-reared) during two phases of the mentoring process (San Diego Wild Animal Park versus release sites). Of the 17 behaviors examined by 2 x 2 analyses of variance (ANOVAs), two significant interactions between the rearing method and mentoring phase were found: pulls feathers and feeds alone. For both behaviors, parent-reared condors engaged in these activities more often at the zoo and less often at the release pens than did the puppet-reared condors. The main effect of rearing was also significant for two behaviors: near others, and receives contact aggression from other. Parent-reared birds were more likely to be near another bird and receive contact aggression, regardless of mentoring phase, than puppet-reared birds. The effect size for 16 of the 17 behaviors was greater for the rearing method than for mentoring phase. Rearing method differences may persist long-term, as parent-reared adult mentors were significantly more aggressive than puppet-reared adult mentors. Dominance relations were examined for both cohorts, with the first cohort exhibiting a strong linear relationship (h' = 0.86, P = 0.018), whereas the second cohort exhibited a moderate but non-significant linear hierarchy (h' = 0.63, P = 0.21). The rearing method had no effect on dominance among the juveniles, but adults were probably dominant to juveniles (P = 0.052; the difference was nearly significant). Although social behaviors between the two rearing groups were similar in most respects, this study is the first to document measurable differences between puppet- and parent-reared captive-bred California condor juveniles. Zoo Biol 27:1-18, 2008. (c) 2007 Wiley-Liss, Inc.

Increased frequency of multiradial chromosome structures in mouse embryonic fibroblasts lacking functional Werner syndrome protein and poly(ADP-ribose) polymerase-1.

To determine whether the mouse Werner syndrome homologue (Wrn) and the poly (ADP-ribose) polymerase-1 (PARP-1) enzymes act in concert to prevent specific chromosomal rearrangements, mice with a mutation in the helicase domain of the Wrn gene (Wrn(Deltahel/Deltahel) mice) were crossed to PARP-1 null mice. Spectral karyotyping of the mouse metaphases was used in correlation with conventional G-banded karyotype analysis to precisely define the chromosomal aberrations in cells. Although there was no recurrent clonal chromosome aberration, PARP-1 null/Wrn(Deltahel/Deltahel) fibroblasts were distinguished by an increased frequency of chromatid breaks. Interestingly, multiradial structures were the only type of DNA rearrangement that was significantly higher in such PARP-1 null/Wrn(Deltahel/Deltahel) cells. These results indicate that Wrn and PARP-1 enzymes may be part of a protein complex involved in the processing of DNA breaks that can ultimately lead to multiradial structures when both enzymes are nonfunctional. Finally, regions of chromosomes known to be fragile sites in the mouse genome are not more prone to DNA rearrangements in the absence of both PARP-1 and functional Wrn proteins. Moreover, the low number of recurrent rearranged chromosome at any given site suggest a random mutagenesis process in PARP-1 null/Wrn(Deltahel/Deltahel) fibroblasts.

Experimental integrative muscular movement technique enhances cervical range of motion in patients with chronic neck pain: a pilot study.

INTRODUCTION: Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in women of occupation age, the largest demographic group with neck pain. METHODS: A total of 38 women were assigned to IMMT (n=28) or Swedish massage (n=10) in a blinded manner. Both groups received eight 30-minute treatments over 4 weeks. Cervical range of motion (ROM) in flexion, extension, sidebending, and rotation was measured before and after treatment. Each patient's pain was assessed by using an analogue pain scale of 0-10. RESULTS: Compared with the Swedish massage group, patients receiving IMMT experienced a significant increase in ROM in cervical flexion (p<0.001), extension (p<0.001), sidebending (p<0.05), and rotation (p<0.001). Absolute change in pain for IMMT was -1.75 units compared with -0.3 units for Swedish massage (p<0.05). CONCLUSION: Patients receiving the IMMT demonstrated significantly improved cervical ROM in every movement measured compared with Swedish massage. Inclusion of the IMMT in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes in patients with neck pain.

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.

BACKGROUND: There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). METHODS: The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. RESULTS: T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. CONCLUSIONS: This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.

Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer.

INTRODUCTION: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. METHODS: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. RESULTS: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. CONCLUSIONS: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.

Seeing through The Bell Jar: investigating linguistic patterns of psychological disorder.

As a means of conveying difficult personal experiences, illness narratives and their analysis have the potential to increase awareness of patients' lives and circumstances. Becoming sensitised to the linguistic texture of narrative offers readers a means of increasing narrative understanding. Using the fictional narrative of The Bell Jar, this paper outlines a novel method for exploring the language of illness narratives. Corpus stylistics provides new insights into narrative texture and demonstrates the importance of recurrent linguistic features in shaping meaning. The paper concludes by proposing the application of a similar methodology to non-fictional illness narratives in therapeutic contexts.

A novel massage therapy technique for management of chronic cervical pain: a case series.

BACKGROUND: Neck pain is a generalized condition resulting from a complex etiology with presentation of a wide variety of symptoms. Neck pain is most often accompanied by decreased range of motion (ROM), muscle and joint stiffness, and limitations in functional capabilities. This condition may result in significant personal and societal burden. PURPOSE: We evaluated the effectiveness of a novel massage therapy intervention by following the treatment regimen and outcomes of two patients experiencing chronic neck pain. PARTICIPANTS: Two patients (46 and 53 years old) experienced chronic (>5 years) neck pain. Both patients reported pain, limited ROM, and muscle and joint stiffness. Additionally, the first patient reported a lack of sleep, and both patients stated their pain interfered with their quality of life and activities of daily living. INTERVENTION: Patients received the Integrative Muscular Movement Technique (IMMT) intervention approximately twice a week for a total of eight treatments, each approximately 20 minutes in duration. RESULTS: Both patients experienced a reduction in pain and an increase in cervical ROM in flexion, extension, rotation, and sidebending. The first patient also reported an increased ability to sleep. Both patients reported an increased ability to perform activities of daily living, including work-related responsibilities. CONCLUSIONS: For the two patients included in this report, therapist observations and patient reports indicate that inclusion of the IMMT treatment in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes of these patients.

A genetic approach to stratification of risk for age-related macular degeneration.

The genetic determinants of age-related macular degeneration (AMD) are reviewed and a novel approach to risk determination based upon inherited genetic polymorphisms and smoking history is presented. Although AMD was long thought to have primarily an environmental etiology, genetic variation is now known to account for the majority of the disease risk, with variations in the genes of the complement pathways playing a prominent role. Independent and validated clinical studies have implicated the C3 gene and its regulator, complement factor H (1q31.1), complement component 2 (6q21.33), and complement factor B (6q21.33). Subtle variations in complement activity increase the risk of symptomatic macular inflammation with age. A second group of AMD-associated genetic markers may aggravate complement-mediated inflammation by permitting retinal oxidative damage. Variation within the chromosomal site (10q26) coding a mitochondrial-associated protein (age-related maculopathy susceptibility 2) and an independent variation within the mitochondrial genome itself (A4917G) suggest a contributing pathophysiological role of retinal oxidative stress. A genetic panel of disease-susceptibility markers and smoking history can identify a group of individuals with greater than 65% lifetime risk of AMD. The introduction of genetic marker testing into clinical practice may identify patients with early disease who may be aided by presymptomatic monitoring or inclusion into trials of newer prophylactic agents.

Clinically detectable copy number variations in a Canadian catchment population of schizophrenia.

Copy number variation (CNV) is a highly topical area of research in schizophrenia, but the clinical relevance is uncertain and the translation to clinical practice is under-studied. There is a paucity of research involving truly community-based samples of schizophrenia and widely available laboratory techniques. Our objective was to determine the prevalence of clinically detectable CNVs in a community sample of schizophrenia, while mimicking typical clinical practice conditions. We used a brief clinical screening protocol for developmental features in adults with schizophrenia for identifying individuals with 22q11.2 deletions and karyotypically detectable chromosomal anomalies in 204 consecutive patients with schizophrenia from a single Canadian catchment area. Twenty-seven (13.2%) subjects met clinical criteria for a possible syndrome, and 26 of these individuals received clinical genetic testing. Five of these, representing 2.5% of the total sample (95% CI: 0.3%-4.6%), including two of ten patients with mental retardation, had clinically detectable anomalies: two 22q11.2 deletions (1.0%), one 47, XYY, and two other novel CNVs--an 8p23.3-p23.1 deletion and a de novo 19p13.3-p13.2 duplication. The results support the utility of screening and genetic testing to identify genetic syndromes in adults with schizophrenia in clinical practice. Identifying large, rare CNVs (particularly 22q11.2 deletions) can lead to significant changes in management, follow-up, and genetic counselling that are helpful to the patient, family, and clinicians.

A male phenotype with Aicardi syndrome.

Aicardi syndrome is a rare neurodevelopmental condition that occurs almost exclusively in women. We report a second male phenotype and 47,XXY karyotype with a typical presentation of the Aicardi syndrome including a midline arachnoid cyst.

Diet and the environment: does what you eat matter?

Food demand influences agricultural production. Modern agricultural practices have resulted in polluted soil, air, and water; eroded soil; dependence on imported oil; and loss of biodiversity. The goal of this research was to compare the environmental effect of a vegetarian and nonvegetarian diet in California in terms of agricultural production inputs, including pesticides and fertilizers, water, and energy used to produce commodities. The working assumption was that a greater number and amount of inputs were associated with a greater environmental effect. The literature supported this notion. To accomplish this goal, dietary preferences were quantified with the Adventist Health Study, and California state agricultural data were collected and applied to state commodity production statistics. These data were used to calculate different dietary consumption patterns and indexes to compare the environmental effect associated with dietary preference. Results show that, for the combined differential production of 11 food items for which consumption differs among vegetarians and nonvegetarians, the nonvegetarian diet required 2.9 times more water, 2.5 times more primary energy, 13 times more fertilizer, and 1.4 times more pesticides than did the vegetarian diet. The greatest contribution to the differences came from the consumption of beef in the diet. We found that a nonvegetarian diet exacts a higher cost on the environment relative to a vegetarian diet. From an environmental perspective, what a person chooses to eat makes a difference.

Contingency awareness in human aversive conditioning involves the middle frontal gyrus.

In contrast to the wealth of data describing the neural mechanisms underlying classical conditioning, we know remarkably little about the mechanisms involved in acquisition of explicit contingency awareness. Subjects variably acquire contingency awareness in classical conditioning paradigms, in which they are able to describe the temporal relationship between a conditioned cue and its outcome. Previous studies have implicated the hippocampus and prefrontal cortex in the acquisition of explicit knowledge, although their specific roles remain unclear. We used functional magnetic resonance imaging to track the trial-by-trial acquisition of explicit knowledge in a concurrent trace and delay conditioning paradigm. We show that activity in bilateral middle frontal gyrus and parahippocampal gyrus correlates with the accuracy of explicit contingency awareness on each trial. In contrast, amygdala activation correlates with conditioned responses indexed by skin conductance responses (SCRs). These results demonstrate that brain regions known to be involved in other aspects of learning and memory also play a specific role, reflecting on each trial the acquisition and representation of contingency awareness.

Working memory and fear conditioning.

Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye-blink conditioning [Clark, R. E. & Squire, L. R. (1998) Science 280, 77-81; Lovibond, P. F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Processes 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the conditioned stimulus (CS) and the onset of the unconditioned stimulus (US). In delay conditioning, the CS and US overlap. We here investigate the extent to which human classical fear conditioning depends on working memory. Subjects had to carry out an n-back task, requiring tracking an item 1 or 2 back in a sequentially presented list of numbers, while simultaneously being tested for their ability to associate auditory cues with shocks under a variety of conditions (single-cue versus differential; delay versus trace; no task versus 0-, 1-, and 2-back). Differential delay conditioning proved to be more resilient than differential trace conditioning but does show a reduction due to task interference similar in slope to that found in trace conditioning. Explicit knowledge of the stimulus contingency facilitates but does not guarantee trace conditioning. Only the single-cue delay protocol shows conditioning during the more difficult working memory task. Our findings suggest that the larger the cognitive demands on the system, the less likely conditioning occurs. A postexperimental questionnaire showed a positive correlation between conditioning and awareness for differential trace conditioning extinction.