A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells.

In normal tissue homeostasis, bidirectional communication between different cell types can shape numerous biological outcomes. Many studies have documented instances of reciprocal communication between fibroblasts and cancer cells that functionally change cancer cell behavior. However, less is known about how these heterotypic interactions shape epithelial cell function in the absence of oncogenic transformation. Furthermore, fibroblasts are prone to undergo senescence, which is typified by an irreversible cell cycle arrest. Senescent fibroblasts are also known to secrete various cytokines into the extracellular space; a phenomenon that is termed the senescence-associated secretory phenotype (SASP). While the role of fibroblast-derived SASP factors on cancer cells has been well studied, the impact of these factors on normal epithelial cells remains poorly understood. We discovered that treatment of normal mammary epithelial cells with conditioned media from senescent fibroblasts (SASP CM) results in a caspase-dependent cell death. This capacity of SASP CM to cause cell death is maintained across multiple senescence-inducing stimuli. However, the activation of oncogenic signaling in mammary epithelial cells mitigates the ability of SASP CM to induce cell death. Despite the reliance of this cell death on caspase activation, we discovered that SASP CM does not cause cell death by the extrinsic or intrinsic apoptotic pathway. Instead, these cells die by an NLRP3, caspase-1, and gasdermin D-dependent induction of pyroptosis. Taken together, our findings reveal that senescent fibroblasts can cause pyroptosis in neighboring mammary epithelial cells, which has implications for therapeutic strategies that perturb the behavior of senescent cells.

Reading direction and spatial effects in parity and arithmetic tasks.

This study investigated the relationship between numerical and spatial processing and reading direction, conducting conceptual replications of the Shaki et al. (Psychonomic Bulletin & Review 16(2): 328-331, 2009) parity task and the Mathieu et al. (Cognition 146: 229-239, 2016, Experiment 1) simple addition (e.g., 3 + 2) and subtraction (e.g., 3 - 2) task. Twenty-four left-to-right readers (LTR) and 24 right-to-left readers (RTL) were tested. The response time (RT) analysis of the parity task presented a robust spatial-numerical association of response codes (SNARC) effect (left-side response advantage for smaller numbers and right-side advantage for larger numbers) for LTR but not RTL readers. In the arithmetic task, the three problem elements (e.g., 3 + 4) were presented sequentially with the second operand displaced slightly to the left or right of fixation. RTL but not LTR readers presented a RT advantage for subtraction relative to addition with a right-shifted second operand compared to it being left-shifted. This is consistent with a spatial bias linked to native reading direction. For both reading-direction groups, effects of the left vs. right side manipulation in the arithmetic or parity task did not correspond to parallel effects in the other task. The results imply that the parity-based SNARC effects and side-related effects in cognitive arithmetic are not equivalent measures of space-related processes in cognitive number processing and likely reflect distinct mechanisms.

Transfer of training in alphabet arithmetic.

In recent years, several researchers have proposed that skilled adults may solve single-digit addition problems (e.g., 3 + 1 = 4, 4 + 3 = 7) using a fast counting procedure. Practicing a procedure, however, often leads to transfer of learning to unpracticed items; consequently, the fast counting theory was potentially challenged by subsequent studies that found no generalization of practice for simple addition. In two experiments reported here (Ns = 48), we examined generalization in an alphabet arithmetic task (e.g., B + 5 = C D E F G) to determine that counting-based procedures do produce generalization. Both experiments showed robust generalization (i.e., faster response times relative to control problems) when a test problem's letter augend and answer letter sequence overlapped with practiced problems (e.g., practice B + 5 = C D E F G, test B + 3 = C D E ). In Experiment 2, test items with an unpracticed letter but whose answer was in a practiced letter sequence (e.g., practice C + 3 = DEF, test D + 2 = E F) also displayed generalization. Reanalysis of previously published addition generalization experiments (combined n = 172) found no evidence of facilitation when problems were preceded by problems with a matching augend and counting sequence. The clear presence of generalization in counting-based alphabet arithmetic, and the absence of generalization of practice effects in genuine addition, represent a challenge to fast counting theories of skilled adults' simple addition.

Effects of pitch on auditory number comparisons.

Three experiments investigated interactions between auditory pitch and the numerical quantities represented by spoken English number words. In Experiment 1, participants heard a pair of sequential auditory numbers in the range zero to ten. They pressed a left-side or right-side key to indicate if the second number was lower or higher in numerical value. The vocal pitches of the two numbers either ascended or descended so that pitch change was congruent or incongruent with number change. The error rate was higher when pitch and number were incongruent relative to congruent trials. The distance effect on RT (i.e., slower responses for numerically near than far number pairs) occurred with pitch ascending but not descending. In Experiment 2, to determine if these effects depended on the left/right spatial mapping of responses, participants responded "yes" if the second number was higher and "no" if it was lower. Again, participants made more number comparison errors when number and pitch were incongruent, but there was no distance × pitch order effect. To pursue the latter, in Experiment 3, participants were tested with response buttons assigned left-smaller and right-larger ("normal" spatial mapping) or the reverse mapping. Participants who received normal mapping first presented a distance effect with pitch ascending but not descending as in Experiment 1, whereas participants who received reverse mapping first presented a distance effect with pitch descending but not ascending. We propose that the number and pitch dimensions of stimuli both activated spatial representations and that strategy shifts from quantity comparison to order processing were induced by spatial incongruities.

Retrieval-induced forgetting of multiplication facts and identity rule.

This research investigated retrieval-induced interference between counterpart multiplication (2 × 3 = 6) and addition facts (2 + 3 = 5). Adults (N =72) repeatedly solved either a set of simple addition (0 + 2, 1 + 5, 2 + 3) or multiplication problems (0 × 2, 1 × 5, 2 × 3) during a practice phase and then switched operations during a test phase that included counterparts to the practiced problems and control problems. The paradigm afforded measurement in response time both of inter-operation retrieval-induced forgetting (RIF) and generalization of practice across different problems within operations. The experiment demonstrated generalization of practice for the rule-based 0 + N = N problems (e.g., practicing 0 + 2 facilitated performance on 0 + 7) as well as for problems governed by the multiplicative identity principle (1 × N = N) and zero-product principle (0 × N = 0), but not the fact-based 1 + N problems. The experiment also demonstrated for the first time inter-operation RIF of fact-based multiplication, which was as large as the effect observed for fact-based addition. The 0 × N, 0 + N, and 1 + N problems did not present item-specific RIF from practice of cross-operation counterparts, but 1 × N problems did, despite the generalization-of-practice evidence that 1 × N problems were solved using an item-general procedure. The item-specific RIF for 1 × N = N must reflect item-specific interference rather than item-level competitor inhibition given that there is no item-level representation of 1 × N = N facts in long-term memory.

A Case With Twists and Turns: A Report of Vertebrobasilar Dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a rare anatomical abnormality of the vertebral artery system, defined as irregular expansion, elongation, and tortuosity of vertebral arteries. Anomalies of the vertebrobasilar artery can have a wide variety of clinical presentations, ranging from simple headaches to debilitating strokes. We present the case of an atypical presentation of VBD which mimicked trigeminal neuralgia by compressing the trigeminal nerve. There are currently no guidelines concerning the management of VBD, nor is there evidence of a definitive cure. This case invoked discussions among the medical team as to whether management should be medically or surgically focused, as well as long-term outcomes for patients with VBD. The superiority of medical versus surgical treatment of this issue is still a debated topic. This patient trialed medical management with dexamethasone and carbamazepine with no improvement in symptoms. He then underwent surgical gamma knife treatment but even this invasive measure was unsuccessful at relieving his symptoms. We hope that by presenting this case, we can display how the therapies available for VBD are limited and often unsuccessful in relieving the disease burden in patients with VBD.

Gonorrheal and chlamydia yield for genital and extragenital testing in children evaluated for sexual abuse.

OBJECTIVE: Texas Forensic Nurse Examiners (TXFNE) performs routine testing of genital and non-genital sites for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), and further testing for other sexually transmitted pathogens. The current Centers for Disease Control and Prevention (CDC) guidelines recommend that testing be based primarily on patient history of type of sexual contact, patient age, community prevalence of sexually transmitted infections (STIs), perpetrator risk factors for STIs, and patient symptoms (Centers for Disease Control and Prevention, 2021). In this study, we were interested in determining whether our practice of testing all sites in all prepubertal patients presenting for sexual abuse for CT and NG resulted in identification of infections that would have been missed if testing had been limited to disclosed sites of sexual contact. METHODS: We conducted a retrospective chart review of all children younger than 14 years who presented to a clinical or hospital site for evaluation by TXFNE in Harris County or surrounding counties during the period January 2020-December 2021. RESULTS: Of the 675 patients tested, 61 patients (9 %) had genital injuries and 45 patients (7 %) had either reported symptoms or examination findings consistent with possible STI infection. There were 11 patients who had positive gonorrhea and/or chlamydia results. Of the 11 patients with a positive result, 10 patients' reported history of type of contact did not fully match sites that tested positive. Diagnosis of STI infection would have been missed for 5 patients if testing had been limited to the disclosed sites of sexual contact. CONCLUSION: Positive results for CT and NG at undisclosed body sites in children presenting with concern for sexual abuse most likely represent infection from sexual contact. Limiting STI testing based on disclosed contact may lead to missed NG and CT infections in prepubertal patients with concern for sexual abuse. This can lead to delayed treatment of the infection and a missed opportunity to ensure the safety of the child.

The N3 is sensitive to odd-even congruency information in arithmetic fact retrieval.

This study investigated the behavioral and electrophysiological effects elicited by adults' simple addition verification when false answers agree or disagree with the odd-even status of the correct sum (parity congruency vs. parity incongruency), while they are near or far from correct (small vs. large splits). Event-related brain potentials were recorded from 18 students using a first-answer-then-problem paradigm. The results showed that odd-even congruency had a significant effect on the N3 latency with a small, but not a large split. Specifically, odd-even congruent answers with a small split elicited an N3 with a longer latency. Analyses of RT similarly indicated a bigger parity-congruency effect with small-split answers compared with large-split answers. This pattern parallels the corresponding effects on N3 and confirms that the N3 is sensitive to odd-even information in arithmetic fact retrieval and that there are clear links between the event-related brain potential pattern and behavioral effects.

To Transfuse or Not to Transfuse: A Case of Unresectable Renal Cell Carcinoma-Induced Warm Autoimmune Hemolytic Anemia.

Warm autoimmune hemolytic anemia (WAIHA) is a rare disease. Roughly half of all cases are considered either primary or idiopathic. The remaining cases are typically secondary to a drug reaction or an underlying disease state such as malignancy, infection, or chronic autoimmune disease. Treatments for WAIHA include corticosteroids, intravenous immunoglobulin (IVIG), rituximab, and splenectomy. We present a case of WAIHA with underlying clear cell renal cell carcinoma (RCC) that was unresectable, creating a difficult treatment course. A 76-year-old male with recently diagnosed clear cell RCC was admitted with symptomatic WAIHA and significant hemodynamic instability. Over the course of his admission, he received 25 blood transfusions, erythropoietin, methylprednisolone, IVIG, rituximab, and mycophenolate mofetil in an attempt to control his disease state. He suffered end-organ damage in the form of heart failure with reduced ejection fraction. He was deemed too unstable for RCC resection or interventional cardiac procedures. Determining an appropriate transfusion threshold proved to be a noteworthy challenge. His hemoglobin eventually stabilized to 7.4 g/dL upon discharge over the course of 27 days of treatment. The underlying cause of his WAIHA was believed to be most likely secondary to RCC. WAIHA may have a prolonged treatment course with high risk of mortality if the underlying cause is not resolvable. If this is the case, it can be difficult to determine a hemoglobin transfusion threshold that maintains normal vital signs while minimizing the risk of transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). Prolonged hemodynamic instability may result in end-organ damage. For our patient, we aimed for a hemoglobin transfusion threshold of 5.0-6.0 g/dL based on his mean arterial pressure (MAP), heart rate, and subjective symptoms.

A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells.

In normal tissue homeostasis, bidirectional communication between different cell types can shape numerous biological outcomes. Many studies have documented instances of reciprocal communication between fibroblasts and cancer cells that functionally change cancer cell behavior. However, less is known about how these heterotypic interactions shape epithelial cell function in the absence of oncogenic transformation. Furthermore, fibroblasts are prone to undergo senescence, which is typified by an irreversible cell cycle arrest. Senescent fibroblasts are also known to secrete various cytokines into the extracellular space; a phenomenon that is termed the senescence-associated secretory phenotype (SASP). While the role of fibroblast derived SASP factors on cancer cells has been well studied, the impact of these factors on normal epithelial cells remains poorly understood. We discovered that treatment of normal mammary epithelial cells with conditioned media (CM) from senescent fibroblasts (SASP CM) results in a caspase-dependent cell death. This capacity of SASP CM to cause cell death is maintained across multiple senescence-inducing stimuli. However, the activation of oncogenic signaling in mammary epithelial cells mitigates the ability of SASP CM to induce cell death. Despite the reliance of this cell death on caspase activation, we discovered that SASP CM does not cause cell death by the extrinsic or intrinsic apoptotic pathway. Instead, these cells die by an NLRP3, caspase-1, and gasdermin D (GSDMD)-dependent induction of pyroptosis. Taken together, our findings reveal that senescent fibroblasts can cause pyroptosis in neighboring mammary epithelial cells, which has implications for therapeutic strategies that perturb the behavior of senescent cells.

Semantic alignment and number comparison.

Are the quantity representations activated by Arabic digits influenced by semantic context? We developed a novel paradigm to examine semantic alignment effects (e.g., Bassok et al. in J Exp Psychol Learn Mem Cogn 34:343-352, 2008) in number comparison. A horizontal word pair (either less more or few many) appeared for 480 ms to prime either relative magnitude (less more) or quantity (few many). Then a horizontal pair of single digits that were either successors (near) or differed by at least four (far) appeared above the word pair. Participants indicated verbally whether or not the word and digit pairs were congruent with respect to left-to-right ascending or descending relative magnitude. The RT advantage for far number pairs compared to near pairs (the distance effect) was greater with magnitude primes (81 ms) than quantity primes (17 ms), demonstrating a semantic alignment effect. This effect disappeared in Experiment 2 in which participants received identical stimuli but named the larger of the two digits and were free to ignore the primes. Nonetheless, mean RT in Experiment 2 was faster with prime and target pairs both ascending or both descending, but only with quantity primes. This prime-dependent order-congruity effect suggests that semantic alignment with respect to numerical order affected number comparison in Experiment 2. The results thereby demonstrate that number comparison exhibits task-dependent semantic alignment effects and recruits distinct numerical representations as a function of semantic context (e.g., Cohen Kadosh and Walsh in Behav Brain Sci 32:313-373, 2009).

MorePower 6.0 for ANOVA with relational confidence intervals and Bayesian analysis.

MorePower 6.0 is a flexible freeware statistical calculator that computes sample size, effect size, and power statistics for factorial ANOVA designs. It also calculates relational confidence intervals for ANOVA effects based on formulas from Jarmasz and Hollands (Canadian Journal of Experimental Psychology 63:124-138, 2009), as well as Bayesian posterior probabilities for the null and alternative hypotheses based on formulas in Masson (Behavior Research Methods 43:679-690, 2011). The program is unique in affording direct comparison of these three approaches to the interpretation of ANOVA tests. Its high numerical precision and ability to work with complex ANOVA designs could facilitate researchers' attention to issues of statistical power, Bayesian analysis, and the use of confidence intervals for data interpretation. MorePower 6.0 is available at https://wiki.usask.ca/pages/viewpageattachments.action?pageId=420413544 .

Neighborhood consistency and memory for number facts.

Verguts and Fias (Memory & Cognition 33:1-16, 2005a) proposed a new model of memory for simple multiplication facts (2 x 3 = 6; 8 x 7 =56) in which learning and performance is governed by the consistency of a problem's correct product with neighboring products in the times table. In the present study, to directly investigate effects of neighborhood consistency, participants memorized a set of 16 novel "pound" arithmetic equations. The pound arithmetic table included eight tie equations with repeated operands (e.g., 4 # 4 = 29) and eight nontie equations (e.g., 5 # 4 = 39). In the consistent problem set, tie and nontie answers in adjacent columns and rows shared a common decade or unit value. In the inconsistent problem set, neighboring tie and nontie problems did not share a common decade or unit. Across 14 study-test blocks, memorization of the pound arithmetic table presented a robust effect of neighborhood consistency, with the rate of learning nearly doubling that of the inconsistent condition. An analysis of error types showed that consistency fostered the development of a categorical structure based on problem operands and that tie problems were encoded as a distinct subcategory of problems. There was also a substantial learning advantage for tie problems relative to nonties both with consistent and inconsistent neighbors. The results indicate that neighborhood consistency can have a major impact on memory for number facts.

Implementation of a comprehensive intervention focused on hospitalized patients with HIV by an existing stewardship program: successes and lessons learned.

BACKGROUND: Several national organizations have advocated for inpatient antiretroviral stewardship to prevent the consequences of medication-related errors. This study aimed to evaluate the impact of a stewardship initiative on outcomes in people with HIV (PWH). METHODS: A pharmacist-led audit and review of adult patients admitted with an ICD-10 code for HIV was implemented to an existing antimicrobial stewardship program. A quasi-experimental, retrospective cohort study was conducted comparing PWH admitted during pre- and post-intervention periods. Rates of antiretroviral therapy (ART)-related errors and infectious diseases (ID) consultation with linkage to care were evaluated through selection of a random sample of patients receiving ART in each period. Length of stay (LOS) and mortality were assessed by analyzing all admissions in the post-intervention period. Clinical outcomes including LOS, 30-day all-cause hospital readmission, and in-hospital and 30-day mortality in the post-intervention group were stratified by patients not on ART, on ART at admission, and started on ART as a result of the intervention. RESULTS: A total of 100 patients in the pre-intervention period and 103 patients in the post-intervention period were included to assess ART-related errors and linkage to care. A reduction in errors (70.0 versus 25.7%, p < 0.001) and increased linkage to care (19.0 versus 39.6%, p < 0.01) were demonstrated. Of 389 admissions during the post-intervention period, 30-day mortality rates were similar between PWH on ART at admission and those initiated on ART during admission (5% versus 8%, respectively), but less than those not on ART (21%). A longer LOS was observed in the patients started on ART during admission (5 days if ART started during admission versus 3 days if not started during admission, p < 0.01). CONCLUSIONS: This interdisciplinary intervention was successful in reducing inpatient ART-related errors and increasing ID consultation with linkage to care among PWH.

Cross-Reactive SARS-CoV-2 Neutralizing Antibodies From Deep Mining of Early Patient Responses.

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.

Bruton's tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor alpha production.

Lipopolysaccharide (LPS), a product of Gram-negative bacteria, is potent mediator of tumor necrosis factor (TNF)alpha production by myeloid/macrophage cells. Inhibitors capable of blocking the signaling events that result in TNF alpha production could provide useful therapeutics for treating septic shock and other inflammatory diseases. Broad spectrum tyrosine inhibitors are known to inhibit TNF alpha production, however, no particular family of tyrosine kinases has been shown to be essential for this process. Here we show that the Bruton's tyrosine kinase (Btk)-deficient mononuclear cells from X-linked agammaglobulinemia patients have impaired LPS-induced TNF alpha production and that LPS rapidly induces Btk kinase activity in normal monocytes. In addition, adenoviral overexpression of Btk in normal human monocytes enhanced TNF alpha production. We examined the role of Btk in TNF alpha production using luciferase reporter adenoviral constructs and have established that overexpression of Btk results in the stabilization of TNF alpha mRNA via the 3' untranslated region. Stimulation with LPS also induced the activation of related tyrosine kinase, Tec, suggesting that the Tec family kinases are important components for LPS-induced TNF alpha production. This study provides the first clear evidence that tyrosine kinases of the Tec family, in particular Btk, are key elements of LPS-induced TNF alpha production and consequently may provide valuable therapeutic targets for intervention in inflammatory conditions.

Mutagenesis of the modified bases, m(5)U1939 and psi2504, in Escherichia coli 23S rRNA.

Ribosomal RNAs (rRNAs) from all kingdoms contain a variety of post-transcriptional modifications and these are typically clustered in the functional centers of the ribosome. The functions of two bases in the 23S rRNA of Escherichia coli that are post-transcriptionally modified, m(5)U1939 and psi2504, were examined by mutagenesis of the rRNA bases and by inactivation of the RumA methylase that methylates U1939. Base substitutions at U1939 had little effect on growth or the fidelity of translation, but altered the sensitivity of the ribosomes to the antibiotics fusidic acid and capreomycin. Strains lacking the RumA methylase were gradually out-competed by wild type strains in growth competition experiments, suggesting that the m(5)U methylation improves ribosome performance. Base changes at psi2504 had dramatic effects on growth and resistance to several peptidyltransferase inhibitor antibiotics and increased the levels of translational errors. The results link these sites of post-transcriptional modification with the ribosome's response to antibiotics and the control of translational fidelity.

Chromosomal alterations in pure nonneoplastic breast lesions: implications for breast cancer progression.

INTRODUCTION: Columnar cell lesions (CCL) and atypical ductal hyperplasia (ADH) frequently coexist and share molecular changes with in situ and invasive components, suggesting that CCL and ADH may be precursors to breast cancer. These conclusions are largely based on studies examining CCL and/or ADH from patients diagnosed with more advanced disease. We assessed allelic imbalance (AI) in pure CCL or ADH specimens to characterize molecular changes in nonneoplastic breast lesions. METHODS: DNA samples were obtained from laser-microdissected pure CCL (n = 42) or ADH (n = 31). AI was assessed at 26 chromosomal regions commonly altered in breast cancer. Data were analyzed using Fisher's exact and Student's t-tests using a cutoff of P < 0.05. RESULTS: The average AI frequency was 6.2% in CCL and 6.1% in ADH; approximately 33% of nonneoplastic lesions had no detectable genetic changes. Levels of AI in CCL and ADH were significantly (P < 0.0001) lower than observed in either low- or high-grade ductal carcinoma in situ (DCIS) lesions. Genetic changes characteristic of in situ and invasive disease, especially on chromosomes 16q and 17p, were infrequent in pure nonneoplastic lesions. CONCLUSIONS: Pure CCL and ADH lesions demonstrate lower levels of genetic alterations than DCIS, invasive carcinomas or CCL/ADH lesions from cancerous breasts; alterations of chromosomes 16q and 17p were not detected. Pure CCL and ADH lesions are not genetically advanced, and molecular profiles do not support these lesions as obligatory precursors to more advanced disease. Molecular differences between pure and synchronous lesions support re-evaluation of current models of disease initiation, progression, and risk.

Switch costs and the operand-recognition paradigm.

Experimental research in cognitive arithmetic frequently relies on participants' self-reports to discriminate solutions based on direct memory retrieval from use of procedural strategies. Given concerns about the validity and reliability of strategy reports, Thevenot et al. in Mem Cogn 35:1344-1352, (2007) developed the operand-recognition paradigm as an objective measure of arithmetic strategies. Participants performed addition or number comparison on two sequentially presented operands followed by a speeded operand-recognition task. Recognition times increased with problem size following addition but not comparison. Thevenot et al. argued that the complexity of addition strategies increases with problem size. A corresponding increase in operand-recognition time occurs because, as problem size increases, working memory contains more numerical distracters. However, because addition is substantially more difficult than comparison, and difficulty increases with problem size for addition but not comparison, their findings could be due to difficulty-related task-switching costs. We repeated Thevenot et al. (Experiment 1) but added a control condition wherein participants performed a parity (odd or even) task instead of operand recognition. We replicated their findings for operand recognition but found robust, albeit smaller, effects of addition problem size on parity judgements. The results indicate that effects of strategy complexity in the operand-recognition paradigm are confounded with task-switching effects, which complicates its application as a precise measure of strategy complexity in arithmetic.

What is learned in procedural learning? The case of alphabet arithmetic.

This research pursued a fine-grained analysis of the acquisition of a procedural skill. In two experiments (n = 29 and n = 27), adults practiced 12 alphabet arithmetic problems (e.g., C + 3 = C D E F) in two sessions with 20 practice blocks in each. If learning reflected speed up of a counting algorithm, response time (RT) speed up should be proportional to the number of counting steps (+ 1, + 2, or + 3). Instead, we found about 50% of RT gains occurred in the first six blocks of practice during which speed up was parallel for + 1, + 2, and + 3 problems. In both experiments, RT initially was a linear function of addend size, reflecting a letter counting strategy. Mean RT for + 3 problems was eventually equal to + 2 problems, which suggests that speed up reflected a gradual shift to associative fact retrieval. Trial by trial strategy self-reports in Experiment 2 revealed that the proportion of trials reported as memory retrieval as opposed to counting predicted 96% of the variance in RT as a function of addend size and practice block. As such, the results provided no evidence for speed up of a counting algorithm and indicated that skill acquisition for this task entailed speed up of task-general processes independent of addend size and rapid transition from counting to fact retrieval. (PsycInfo Database Record (c) 2020 APA, all rights reserved).