HER2-low expression in patients with advanced or metastatic solid tumors.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined category with HER2 1+ or 2+ expression by immunohistochemistry (IHC) and lack of HER2 gene amplification measured by in situ hybridization (ISH). Much remains unknown about the HER2-low status across tumor types and changes in HER2 status between primary and metastatic samples. PATIENTS AND METHODS: HER2 expression by IHC was evaluated in 4701 patients with solid tumors. We have evaluated the HER2 expression by IHC and amplification by ISH in paired breast and gastric/gastroesophageal (GEJ) primary and metastatic samples. HER2 expression was correlated with ERBB2 genomic alterations evaluated by next-generation sequencing (NGS) in non-breast, non-gastric/GEJ samples. RESULTS: HER2 expression (HER2 IHC 1-3+) was found in half (49.8%) of the cancers, with HER2-low (1 or 2+) found in many tumor types: 47.1% in breast, 34.6% in gastric/GEJ, 50.0% in salivary gland, 46.9% in lung, 46.5% in endometrial, 46% in urothelial, and 45.5% of gallbladder cancers. The concordance evaluation of HER2 expression between primary and metastatic breast cancer samples showed that HER2 3+ remained unchanged in 87.1% with a strong agreement between primary and metastatic samples, with a weighted kappa (Κ) of 0.85 (95% confidence interval 0.79-0.91). ERBB2 alterations were identified in 117 (7.5%) patients with non-breast, non-gastric/GEJ solid tumors who had NGS testing. Of 1436 patients without ERBB2 alterations, 512 (35.7%) showed any level HER2 expression by IHC. CONCLUSION: Our results show that HER2-low expression is frequently found across tumor types. These findings suggest that many patients with HER2-low solid tumors might benefit from HER2-targeted therapies.

The Other Shoe: An Early Operant Conditioning Chamber for Pigeons.

We describe an early operant conditioning chamber fabricated by Harvard University instrument maker Ralph Gerbrands and shipped to Japan in 1952 in response to a request of Professor B. F. Skinner by Japanese psychologists. It is a rare example, perhaps the earliest still physically existing, of such a chamber for use with pigeons. Although the overall structure and many of the components are similar to contemporary pigeon chambers, several differences are noted and contrasted to evolutionary changes in this most important laboratory tool in the experimental analysis of behavior. The chamber also is testimony to the early internationalization of behavior analysis.

Nu-Way Snaps and Snap Leads: an Important Connection in the History of Behavior Analysis.

Beginning in the early 1950s, the snap lead became an integral and ubiquitous component of the programming of electromechanical modules used in behavioral experiments. It was composed of a Nu-Way snap connector on either end of a colored electrical wire. Snap leads were used to connect the modules to one another, thereby creating the programs that controlled contingencies, arranged reinforcers, and recorded behavior in laboratory experiments. These snap leads populated operant conditioning laboratories from their inception until the turn of the twenty-first century. They allowed quick and flexible programming because of the ease with which they could be connected, stacked, and removed. Thus, the snap lead was integral to the research activity that constituted the experimental analysis of behavior for more than five decades. This review traces the history of the snap lead from the origins of the snap connector in Birmingham, England, in the late eighteenth century, through the use of snaps connected to wires during the Second World War, to its adoption in operant laboratories, and finally to its demise in the digital age.

Resurgence and Behavioral Contrast, Compared and Contrasted.

This is a review of the relation between operant response resurgence and behavioral contrast. Both are defined by rate changes in a target response as a function of environmental changes spatially or temporally distal to the location of the target response. The typical procedures for investigating these two phenomena differ in that (1) resurgence is studied using concurrent schedules and behavioral contrast predominantly with multiple schedules and (2) resurgence is assessed against an extinction baseline of the target response and behavioral contrast has been assessed under a variety of reinforcement schedules. The distinctions between concurrent and multiple schedules, however, may be ones of degree rather than kind. Research into both phenomena reveals considerable overlap in the controlling variables of the two. With certain caveats, resurgence appears to be an instance of behavioral contrast measured against an extinction baseline. Because of Point 2 above, most instances of behavioral contrast do not meet the definition of resurgence. Investigating resurgence while maintaining target responding by a schedule of reinforcement might be useful, but such a procedure would not qualify as resurgence because it violates the definition of resurgence as the return of a previously reinforced but currently extinguished response. Several implications of the similarities and differences between the two are discussed.

Correction: Resurgence and Behavioral Contrast, Compared and Contrasted.

[This corrects the article DOI: 10.1007/s40614-024-00408-2.].

An analysis of coordinated responding of pigeons.

Experimental analyses of coordinated responding (i.e., cooperation) have been derived from a procedure described by Skinner (1962) in which reinforcers were delivered to a pair of subjects (a dyad) if both responded within a short interval, thus satisfying a coordination contingency. Although it has been suggested that this contingency enhances rates of temporally coordinated responding, limitations of past experiments have raised questions concerning this conclusion. The present experiments addressed some of these limitations by holding the schedule of reinforcement (Experiment 1: fixed ratio 1; Experiment 2; variable interval 20 s) constant across phases and between dyad members and by varying, in different conditions, the number of response keys (one to three) across which coordination could occur. Greater percentages of coordinated responding occurred under the coordinated-reinforcement phases than under independent-reinforcement phases in most conditions. The one exception during the one-key condition of Experiment 1 appeared to be a consequence of variability introduced by the independent-reinforcement phase procedure. Furthermore, coordination percentages decreased with increasing response options under both schedules. These results confirm and extend the finding that coordination contingencies control higher rates of temporally coordinated responding than independent-reinforcement contingencies do.

Response-dependent point loss and response force as disrupting operations on behavioral resistance to change in humans.

Behavioral momentum theory (BMT) provides a theoretical and methodological framework for understanding how differentially maintained operant responding resists disruption. A common way to test operant resistance involves contingencies with suppressive effects, such as extinction or prefeeding. Other contingencies with known suppressive effects, such as response-cost procedures arranged as point-loss or increases in response force, remain untested as disruptive events within the BMT framework. In the present set of three experiments, responding of humans was maintained by point accumulation programmed according to a multiple variable-interval (VI) VI schedule with different reinforcement rates in either of two components. Subsequently, subtracting a point following each response (Experiment 1) or increasing the force required for the response to be registered (Experiments 2 and 3 decreased response rates, but responding was less disrupted in the component associated with the higher reinforcement rate. The point-loss contingency and increased response force similarly affected response rates by suppressing responding and human persistence, replicating previous findings with humans and nonhuman animals when other types of disruptive events (e.g., extinction and prefeeding) were investigated. The present findings moreover extend the generality of the effects of reinforcement rate on persistence, and thus BMT, extending the analysis of resistance to two well-known manipulations used to reduce responding in the experimental analysis of behavior.

A Tale of Two Rats: The Backstory of a Clever Cartoon.

A well-known cartoon among psychologists and behavior analysts depicts two rats in a Skinner box, leaning over a response lever as one says to the other, "Boy, do we have this guy conditioned, every time I press the bar down he drops a pellet in." Anyone who has ever conducted an experiment, worked with a client, or taught someone can relate to the cartoon's message of reciprocal control between subject and experimenter, client and therapist, and teacher and student. This is the tale of that cartoon and its impact. It begins mid-20th-century at Columbia University, then a hotbed of behavioral psychology, which bears an intimate connection to the cartoon's appearance. The tale expands from Columbia to follow the lives of its creators from their undergraduate days there to their deaths decades later. The infusion of the cartoon into American psychology begins with B. F. Skinner, but, over the years, it also has appeared in introductory psychology textbooks and in iterative form in mass media outlets such as the World Wide Web and magazines like The New Yorker. The heart of the tale, however, was stated in the second sentence of this abstract. The tale ends with a review of how reciprocal relations like those depicted by the cartoon's creators have influenced research and practice in behavioral psychology.

Stimulus control of a social operant.

Three pigeon dyads were exposed to a two-component multiple schedule comprised of two tandem variable-interval 30-s interresponse time (IRT) > 3-s schedules in the presence of different stimuli. Pecks to keys by both pigeons of a dyad occurring within 500 ms of one another were required for reinforcement under one tandem schedule (the coordination component), and such coordinated responses were not required under the other (the control component). The terminal link of each schedule ensured that the reinforced coordination response was an IRT > 3 s. Rates of coordinated IRTs > 3 s and total rates of coordinated responses (composed of IRTs > 3 s and IRTs ≤ 3 s) were higher in the coordination components than in either of two different control components in which coordination was not required for reinforcement. This difference in coordinated responses in the presence and absence of the coordination requirement under stimulus control transitorily deteriorated and then was reestablished when the relation between the stimulus and the coordination contingency or its absence was reversed. The results show coordinated responding to function as a discriminated social operant.

Choice dynamics in concurrent ratio schedules of reinforcement.

The generalized matching law predicts performance on concurrent schedules when variable-interval schedules are programmed but is trivially applicable when independent ratio schedules are used. Responding usually is exclusive to the schedule with the lowest response requirement. Determining a method to program concurrent ratio schedules such that matching analyses can be usefully employed would extend the generality of matching research and lead to new avenues of research. In the present experiments, ratio schedules were programmed dependently such that responses to either of the two options progressed the requirement on both schedules. Responding is not exclusive because the probability of reinforcement increases on both schedules as responses are allocated to either schedule. In Experiment 1, performance on concurrent variable-ratio schedules was assessed, and reinforcer ratios were varied across conditions to investigate changes in sensitivity. Additionally, the length of a changeover delay was manipulated. In Experiment 2, performance was compared under concurrently available, dependently programmed variable-ratio and fixed-ratio schedules. Performance was well described by the generalized matching law. Increases in the changeover delay decreased sensitivity, whereas sensitivity was higher when variable-ratio schedules were employed, compared with fixed-ratio schedules. Concurrent ratio schedules can be a viable approach to studying functional differences between ratio and interval schedules.

Confluence of Science and History in the Experimental Analysis of Behavior Course.

This is a review of content and method for incorporating the history of the experimental analysis of behavior (EAB) into the EAB course, although the material also could be adapted for any course related to the topics of learning and behavior change, or the history of psychology. Six elements associated with establishing a new discipline are considered as a framework for introducing the history of EAB: the intellectual leader/founding scientist(s), early proponents of the new area who advance and elaborate on the founder's ideas, the cultural context in which the discipline develops, a set of methods, a textbook, and means of communicating with other, similarly inclined scientists. The historical ebb and flow of research and some of the reasons for these shifts are discussed next, with examples of EAB research themes that have shifted over time. Illustrating the history of EAB with specific milestone experiments seems a useful way to both introduce substantive research and its history. To that end, milestone experiments in EAB are discussed. The review ends with considerations about locating historical material within the EAB course.

Hayne Waring Reese (1931-2022).

Memorializes Hayne Waring Reese (1931-2022). Hayne is remembered for impeccable scholarship, incisive analyses, and broad perspective on psychology. Early in his career, he published seminal analyses of transpositional learning by children. Later, he and Lewis Lipsitt helped solidify experimental child psychology with a textbook of that title. He became editor of the Journal of Experimental Child Psychology in 1983, remaining so until 1997. He also edited the annual Advances in Child Development and Behavior from 1969 to 1999 and books resulting from the WVU Conferences on Life-Span Development from 1969 to 1992. His writings, many with William Overton, on worldviews in psychology are foundational to the field and widely cited. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of signaled and unsignaled delays of reinforcement on response maintenance in zebrafish (Danio rerio).

Effects of delays of reinforcement on zebrafish behavior were examined following training with immediate reinforcement. The delay was either signaled by an exteroceptive stimulus present for the entire delay period (fully signaled), signaled briefly only at delay onset (partial signal), or without a stimulus (unsignaled). Unsignaled delays consistently resulted in low response rates. Fully signaled delays resulted in higher response rates than unsignaled delays when the delay was 3 s, but this difference in response rates disappeared at 6-s delays. Partially signaled delays were less effective in maintaining responding than fully signaled delays, but more effective than unsignaled delays, although these results were only suggestive. These results indicate that stimulus changes that occur during delays to reinforcement have similar effects with zebrafish as with other species, but also that responding of zebrafish has a relatively low tolerance to the delay duration. A vast majority of experiments examining zebrafish behavior suggests that the fish have potential to serve as an interface between biological and behavioral science, but this may not be the case in some research areas involving delays, such as delay discounting.

Grounding applied animal behavior practices in the experimental analysis of behavior.

Some of the earliest applications outside the laboratory of principles derived from the experimental analysis of behavior (EAB), such as the pioneering work of Keller and Marian Breland, involved animals. This translational tradition continues to the present as EAB-related behavior principles are applied with increasing frequency to behavior management and training practices with animals in nonlaboratory settings. Such translations, and those populations to which they are applied, benefit from a rigorous experimental analysis of practices that are promulgated in popular outlets. These translations both affirm the generality of those principles and serve as goads for laboratory and field research that can further articulate extant principles, develop new ones, and refine methods of application and assessment. This review considered several areas of basic EAB research and contemporary applied animal behavior (AAB) practices in relation to one another: (1) response establishment and maintenance, (2) response reduction and elimination, (3) chaining and conditioned reinforcement, and (4) discriminative stimulus control. Within each topic, a selection of processes and procedures in both EAB and AAB work were reviewed in relation to one another.

Resurgence during transitions from variable- to fixed-interval schedules.

The effects of local periods of extinction on resurgence following transitions from variable-interval (VI) to fixed-interval (FI) schedules were studied using four pigeons exposed to a within-session resurgence procedure. Each session was divided into a Training (T) Alternative-Reinforcement (AR), and Resurgence Test (RT) phase. During the T phase, key pecking was reinforced under a VI 60-s schedule on one key. In the AR phase, responses reinforced in the T phase were extinguished, while responses to a different key were reinforced under a VI 90-s schedule. Next, responding to the same key that produced reinforcers in the AR phase was reinforced according to four different RT conditions: RT phase I (FI 90 s), RT phase II (FI 180 s), RT phase III (FI 45 s), or RT phase IV (extinction). The frequency of resurgence generally was an inverse function of the rate of reinforcement in the RT phase. Resurgence occurred less often when reinforcers were delivered under the FI 45-s schedule and more often under leaner schedules in the RT phase, peaking under extinction. The results show that resurgence may occur during local periods of extinction, with larger and more consistent effects occurring when the rate of reinforcement in the RT condition is leaner than it was during the preceding AR phase.

Murray Sidman (1923-2019).

Memorializes Murray Sidman (1923-2019). Murray Sidman wrote the definitive analysis of single-case experimentation, Tactics of Scientific Research: Evaluating Experimental Data in Psychology (1960). The book, never out of print, remains widely used and frequently cited. Sidman, along with B. F. Skinner, Fred Keller, and a few others, founded the field of behavior analysis. His contributions have been widely recognized with numerous award and honors, including an honorary D.Sc. degree from West Virginia University in 2007. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

C-3s and Model Ts: The Machines behind Two Lovely Farewells.

B. F. Skinner's 1976 editorial "Farewell my LOVELY," eulogizing the passing of the cumulative record as a primary form of data analysis, borrowed its title from a 1936 E. B. White essay of the same name. In it, White, a well-known 20th century essayist and children's book author, eulogized the Model T Ford. This article considers the parallels between the machine behind the cumulative record-the cumulative recorder-and White's Model T. The cumulative recorder considered for comparison is the Ralph Gerbrands Company Model C-3, widely considered by scientists of the time to be the best of the cumulative recorders that proliferated between the 1950s and the 1990s. On a much more modest scale, the C-3 became as popular, visible, distinct, and important in research laboratories devoted, but not limited, to the experimental analysis of behavior as was the Model T on the roads of early 20th century America. Not only were there parallels in manufacture and marketing, but, more importantly, in reliability, durability and ease of function of these two machines that changed the respective practices and culture of behavioral psychology and the world.

Correction to: Big Surprises: Jackpot Reinforcers in Research and Practice.

[This corrects the article DOI: 10.1007/s40617-020-00423-0.].

Early-extinction effects on a force response of humans.

Humans were used to investigate changes in response force occurring soon after reinforcement was eliminated. In Experiment 1, in a 300-s baseline phase, 10 participants received a point for holding down a pressure sensor set to operate at a force equal to 85% of the maximum force the participants exerted during a pretest. Following this, during a 600-s extinction phase, criterion responses had no consequence. In Experiment 2, 6 participants worked on the same task, but (a) points were exchangeable for money and (b) after extinction, the reinforcement baseline phase was reinstated. In Experiment 3, 6 participants completed the same task as in Experiment 2, but the required minimum force was 60% of the maximum force exerted during the pretest. In each experiment, increases in response force relative to the mean and peak force exerted during the last 100 s of baseline were observed in most participants when force responses were aggregated into short sample intervals, but less so with longer ones. The increases, however, were not systematic across or within participants, questioning the generality of and the criteria for demonstrating an extinction burst.

What is an extinction burst?: A case study in the analysis of transitional behavior.

Among the tactics of experimental science discussed by Sidman (1960) were those used to study transitional behavior. Drawing from his insights, this review considers an often cited but infrequently analyzed aspect of the transition from reinforcement to extinction: the extinction burst. In particular, the review seeks to answer the question posed in its title. The generic definition of an extinction burst as an increase in response rate following the onset of extinction is found to be wanting, raising more questions than it answers. Because questions of definition in science usually come down to those of measurement, the answer to the title's question is suggested to be found in how behavior prior to extinction is maintained and measured, when and how extinction is introduced, and where in time and how behavior early in extinction is measured. This analysis suggests that a single, uniform, and precise definition of the extinction burst is misguided. Examining how each of these facets contributes to what has been described generically as the extinction burst is a small, but important, part of Sidman's methodological legacy to the experimental analysis of behavior.