The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AIM: While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic. METHODS: A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (eg social distancing, mask wearing) were examined. RESULTS: Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9 ± 1.0 versus 11.6 ± 1.0; p < .001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4 ± 1.4 to 13.3 ± 1.4, p = .024) as did those with higher levels of anxiety (from 11.5 ± 1.1 to 13.6 ± 1.1, p < .001). CONCLUSIONS: Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use. IMPLICATIONS: Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

Using an experimental tobacco marketplace to pilot test the substitutability of JUUL e-cigarettes and other alternative nicotine and tobacco products for conventional cigarettes among vulnerable populations.

The Experimental Tobacco Marketplace (ETM) is an online research marketplace where increasing the cost of cigarettes is used to investigate the substitutability of other fixed-price tobacco products such as electronic nicotine delivery systems (ENDS). The ETM is useful for modeling effects of potential policy changes on use of various concurrently available products. To our knowledge, the ETM has not been used to investigate substitutability of newer generation e-cigarettes or populations at increased risk for smoking, heavy smoking, nicotine dependence, and smoking-attributable adverse effects. In the current pilot study, participants were 30 adult daily smokers with socioeconomic disadvantage or comorbid psychiatric conditions (substance-use disorder or mental illness). In each session, cigarette prices increased ($0.12, $0.25, $0.50, $1.00. and $2.00 per cigarette) while prices for alternative products remained fixed. Across three ETM sessions, either all products, all products except little cigars and cigarillos (LCCs), or all products except ENDS (JUUL e-cigarettes) were available. Linear regression was performed on individual participant data using log-transformed cigarette price to determine demand and substitution. Cigarette demand decreased as price increased across sessions (significantly non-zero slopes, ps ≤ 0.0001). When all products were available, ENDS substitution increased as cigarette price increased (significantly non-zero slope, p = .016). When LCCs were unavailable, ENDS again were a significant substitute (p = .008). When ENDS were unavailable, LCCs did not substitute (ps ≥ 0.48). In all sessions, participants rarely purchased other products (e.g., snus). Overall, ENDS were the most robust substitute for cigarettes, further underscoring the potential importance of ENDS availability on the impact of tobacco regulatory policies.

Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage.

INTRODUCTION: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage. AIMS AND METHODS: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period. RESULTS: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified. CONCLUSIONS: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings. TRIAL REGISTRATION: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered. IMPLICATIONS: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.

Comparing participant estimated demand intensity on the cigarette Purchase Task to consumption when usual-brand cigarettes were provided free.

Accumulating evidence suggests that the hypothetical Cigarette Purchase Task (CPT), especially its demand Intensity index (i.e., estimated cigarettes participants would smoke if free), is associated with individual differences in smoking risk. Nevertheless, few studies have examined the extent to which hypothetical CPT demand Intensity may differ from consumption when participants are provided with free cigarettes. That topic is the overarching focus of the present study. Participants were 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage. CPT was administered for usual-brand cigarettes prior to providing participants with seven days of their usual-brand cigarettes free of cost and consumption was recorded daily via an Interactive Voice Response (IVR) System. Demand Intensity was correlated with IVR smoking rate (rs 0.670-0.696, ps < 0.001) but estimates consistently exceeded IVR smoking rates by an average of 4.4 cigarettes per day (ps < 0.001). Importantly, both measures were comparably sensitive to discerning well-established differences in smoking risk, including greater cigarettes per day among men versus women (F(1,732) = 18.74, p < 0.001), those with versus without opioid-dependence (F(1,732) = 168.37, p < 0.001), younger versus older adults (F(2,730) = 32.93, p < 0.001), and those with lower versus greater educational attainment (F(1,732) = 38.26, p < 0.001). Overall, CPT demand Intensity appears to overestimate consumption rates relative to those observed when participants are provided with free cigarettes, but those deviations are systematic (i.e., consistent in magnitude and direction, Fs all <1.63; ps > 0.19 for all interactions with subgroups). This suggests that demand Intensity was sensitive to established group differences in smoking rate, supporting its utility as an important measure of addiction potential.

Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines.

Human endogenous retrovirus (HERV) sequences make up ~8% of the human genome and increased expression of some HERV proteins has been observed in various pathologies including leukaemia and multiple sclerosis. However, little is known about the function of these HERV proteins or environmental factors which regulate their expression. Silver nanoparticles (AgNPs) are used very extensively as antimicrobials and antivirals in numerous consumer products although their effect on the expression of HERV gene products is unknown. Cell proliferation and cell toxicity assays were carried out on human acute T lymphoblastic leukaemia (MOLT-4) and Fanconi anaemia associated acute myeloid leukaemia (FA-AML1) cells treated with two different sizes of AgNPs (7nm and 50nm diameter). Reverse-transcriptase polymerase chain reaction and western blotting were then used to the assess expression of HERV-W syncytin-1 mRNA and protein in these cells. FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7nm sized AgNp's being the most toxic in these cells. MOLT-4 cell were more resistant and showed no evidence of differential toxicity to the different sized particles. Syncytin-1 mRNA and protein were induced by both 7 and 50nm AgNPs in both cell types yet with different kinetics. In summary, the observation that AgNPs induce expression of syncytin-1 in FA-AML1 and MOLT-4 cells at doses as little as 5 µg/ml is grounds for concern since this protein is up-regulated in both malignant and neurodegenerative diseases. Considering the widespread use of AgNPs in the environment it is clear that their ability to induce syncytin-1 should be investigated further in other cell types.

Increased prevalence of JC polyomavirus in cervical carcinomas from women infected with HIV.

Although subclinical persistent infections with the human polyomaviruses BKV and JCV are ubiquitous worldwide, these are known to vary in relation to diseases present and geographical location. DNAs from 220 cervical smears and 109 invasive cervical carcinomas obtained from HIV positive and HIV negative Kenyan women of known HPV status were analyzed by nested endpoint PCR for BKV and JCV. BKV-JCV DNA was detected in 5/105 (4.7%) of cervical smears and in 6/37 (16%) of cervical carcinomas from women infected with HIV whereas 9/115 (7.8%) of the cervical smears and 4/72 (5.5%) of the carcinomas were positive in HIV negative women. Nested PCR showed that all 24 samples were positive for JCV and not BKV. JCV was not more prevalent in either HPV positive (P = 0.438) or HPV negative women (P = 0.392). However, 37% of carcinomas and smears which were positive for JCV were also positive for a "high-risk" oncogenic HPV. Comparison of the incidence of JCV in cervical smears and cervical carcinomas showed a ∼3-fold increase in samples from HIV positive women with cervical carcinoma (P = 0.025) whereas no significant difference was found between cervical smears and cervical carcinomas from HIV negative women (P = 0.553). These results suggest that JCV may combine with high-risk HPV infection in women infected with HIV to influence the rate of progression to invasive cervical carcinoma.

Federal efforts to define and advance telehealth--a work in progress.

BACKGROUND: The integration of telecommunications and information systems in healthcare is not new or novel; indeed, it is the current practice of medicine and has been an integral part of medicine in remote locations for several decades. The U.S. Government has made a significant investment, measured in hundreds of millions of dollars, and therefore has a strong presence in the integration of telehealth/telemedicine in healthcare. However, the terminologies and definitions in the lexicon vary across agencies and departments of the U.S. Government. The objective of our survey was to identify and evaluate the definitions of telehealth/telemedicine across the U.S. Government to provide a better understanding of what each agency or department means when it uses these terms. METHODOLOGY: The U.S. Government, under the leadership of the Health Resources and Services Administration in the U.S. Department of Health and Human Services, established the Federal Telemedicine (FedTel) Working Group, through which all members responded to a survey on each agency or department's definition and use of terms associated with telehealth. RESULTS AND CONCLUSIONS: Twenty-six agencies represented by more than 100 individuals participating in the FedTel Working Group identified seven unique definitions of telehealth in current use across the U.S. Government. Although many definitions are similar, there are nuanced differences that reflect each organization's legislative intent and the population they serve. These definitions affect how telemedicine has been or is being applied across the healthcare landscape, reflecting the U.S. Government's widespread and influential role in healthcare access and service delivery. The evidence base suggests that a common nomenclature for defining telemedicine may benefit efforts to advance the use of this technology to address the changing nature of healthcare and new demands for services expected as a result of health reform.

Update on Effects of the Prophylactic HPV Vaccines on HPV Type Prevalence and Cervical Pathology.

Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location-presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices.

Plexin D1: new potential biomarker for cervical cancer.

To explore possible role of Plexin D1 in cancer angiogenesis with special focus on cervical cancer. Twelve various normal tissues, 12 various tumor samples, and 59 different stages of cervical cancer samples on tissue microarrays were examined for the expression of Plexin D1. The findings of our study clearly indicate that Plexin D1 is strongly associated with cellular differentiation in the tissues investigated, and that expression is strongly dependent on the tumor histotype. In some tumor subtypes, the protein was detected at several-fold higher levels than was found in the corresponding normal tissues, while in others, expression was similar to normal tissues. Most significantly, strong expression was detected in the endothelial cells of the cervical cancer samples, yet no expression was seen in endothelial cells of normal cervical tissues, which suggests a potential role of Plexin D1 in cervical cancer-associated angiogenesis.Regarding the implications of Plexin D1 and its associations with cancer angiogenesis, it might be a potential cervical cancer biomarker if further studies confirm the present preliminary findings.

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.

Delay discounting and narcissism: A meta-analysis with implications for narcissistic personality disorder.

Several psychiatric conditions (e.g., substance use, mood, and personality disorders) are characterized, in part, by greater delay discounting (DD)-a decision-making bias in the direction of preferring smaller, more immediate over larger, delayed rewards. Narcissistic personality disorder (NPD) is highly comorbid with substance use, mood, and other personality disorders, suggesting that DD may be a process underpinning risk for NPD as well. This meta-analysis examined associations between DD and theoretically distinct, clinically relevant dimensions of narcissism (i.e., grandiosity, entitlement, and vulnerability). Literature searches were conducted and articles were included if they were written in English, published in a peer-reviewed journal, contained measures of DD and narcissism and reported their association, and used an adult sample. Narcissism measures had to be systematically categorized according to clinically relevant dimensions (Grijalva et al., 2015; Wright & Edershile, 2018). Seven studies met inclusion criteria (N = 2,705). DD was positively associated with narcissism (r = .21; 95% confidence interval [.10, .32]), with this association being largely attributable to measures of trait grandiosity that were used in each study (r = .24; 95% confidence interval [.11, .37]). No studies included diagnostic NPD assessments. These findings provide empirical evidence that DD is related to trait narcissism and perhaps risk for NPD (e.g., grandiosity listed in Criterion B of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, alternative model of personality disorders). Considering the positive evidence from this review, and the dearth of research examining DD in individuals with NPD, investigators studying NPD may consider incorporating DD measures in future studies to potentially inform clinical theory and novel adjunctive treatment options. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

CK2 Phosphorylation of Human Papillomavirus 16 E2 on Serine 23 Promotes Interaction with TopBP1 and Is Critical for E2 Interaction with Mitotic Chromatin and the Viral Life Cycle.

During the human papillomavirus 16 (HPV16) life cycle, the E2 protein interacts with host factors to regulate viral transcription, replication, and genome segregation/retention. Our understanding of host partner proteins and their roles in E2 functions remains incomplete. Here we demonstrate that CK2 phosphorylation of E2 on serine 23 promotes interaction with TopBP1 in vitro and in vivo and that E2 is phosphorylated on this residue during the HPV16 life cycle. We investigated the consequences of mutating serine 23 on E2 functions. E2-S23A (E2 with serine 23 mutated to alanine) activates and represses transcription identically to E2-WT (wild-type E2), and E2-S23A is as efficient as E2-WT in transient replication assays. However, E2-S23A has compromised interaction with mitotic chromatin compared with E2-WT. In E2-WT cells, both E2 and TopBP1 levels increase during mitosis compared with vector control cells. In E2-S23A cells, neither E2 nor TopBP1 levels increase during mitosis. Introduction of the S23A mutation into the HPV16 genome resulted in delayed immortalization of human foreskin keratinocytes (HFK) and higher episomal viral genome copy number in resulting established HFK. Remarkably, S23A cells had a disrupted viral life cycle in organotypic raft cultures, with a loss of E2 expression and a failure of viral replication. Overall, our results demonstrate that CK2 phosphorylation of E2 on serine 23 promotes interaction with TopBP1 and that this interaction is critical for the viral life cycle. IMPORTANCE Human papillomaviruses are causative agents in around 5% of all cancers, with no specific antiviral therapeutics available for treating infections or resultant cancers. In this report, we demonstrate that phosphorylation of HPV16 E2 by CK2 promotes formation of a complex with the cellular protein TopBP1 in vitro and in vivo. This complex results in stabilization of E2 during mitosis. We demonstrate that CK2 phosphorylates E2 on serine 23 in vivo and that CK2 inhibitors disrupt the E2-TopBP1 complex. Mutation of E2 serine 23 to alanine disrupts the HPV16 life cycle, hindering immortalization and disrupting the viral life cycle, demonstrating a critical function for this residue.

Combining metabolic fingerprinting and footprinting to understand the phenotypic response of HPV16 E6 expressing cervical carcinoma cells exposed to the HIV anti-viral drug lopinavir.

Recently, it has been reported that the anti-viral drug, lopinavir, which is currently used as a human immunodeficiency virus (HIV) protease inhibitor, could also inhibit E6-mediated proteasomal degradation of mutant p53 in E6-transfected C33A cells. In this study, C33A parent control cells and HPV16 E6-transfected cells were exposed to lopinavir at concentrations ranging from 0 to 30 microM. The phenotypic response was assessed by Fourier transform infrared (FT-IR) spectroscopy directly on cells (the metabolic fingerprint) and on the cell growth medium (the metabolic footprint). Multivariate analysis of the data using both principal components analysis (PCA) and canonical variates analysis (PC-CVA) showed trends in scores plots that were related to the concentration of the drug. Inspection of the PC-CVA loadings vector revealed that the effect was not due to the drug alone and that several IR spectral regions including proteins, nucleotides and carbohydrates contributed to the separation in PC-CVA space. Finally, partial least squares regression (PLSR) could be used to predict the concentration of the drug accurately from the metabolic fingerprints and footprints, indicating a dose related phenotypic response. This study shows that the combination of metabolic fingerprinting and footprinting with appropriate chemometric analysis is a valuable approach for studying cellular responses to anti-viral drugs.

The control response in assessing resurgence: Useful or compromised tool?

Resurgence experiments sometimes include an operandum on which a history of reinforcement has not been experimentally established. The purpose of this control operandum is to rule out a generalized increase in responding when the alternative response is extinguished as being the cause of the resurgent target response. A review of the results of experiments conducted with both nonhumans and humans in which a control operandum was included shows that control- operandum responding is more common in the latter and almost nonexistent in the former. Both the presence and absence of responding on the control operandum, however, are subject to multiple interpretations thereby rendering it a compromised tool. Alternatives to using a control operandum to rule out extinction induction as the basis for resurgence include a preresurgence test control procedure and a differential resurgence procedure.

Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines.

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with the ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called "latent" infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.

Resurgence without overall worsening of alternative reinforcement.

Three experiments were conducted with pigeons to assess discriminated periods of nonreinforcement as precipitators of resurgence. Each experiment occurred in three phases. In the Training phase, key-pecking was reinforced according to variable-interval schedules that alternated between two response keys (Experiment 1) or were concurrently available on two response keys (Experiments 2a & 2b). In the Alternative-Reinforcement phase, responding to one key was extinguished, while that to the other was reinforced according to tandem schedules. These then were replaced by chained schedules with the same programmed reinforcement rate in the Resurgence-Test phase. Resurgence occurred both when the signaled period of nonreinforcement was a darkened keylight in the terminal link of the chain schedule (Experiment 1) and a darkened keylight (Experiment 2a) or keylight color change (Experiment 2b) in the initial link of the chain schedule. Thus, signaled periods of extinction, without accompanying reductions in reinforcement rate, precipitated resurgence, suggesting that resurgence is not the result of worsening of overall reinforcement conditions, but also occurs when local conditions of reinforcement are worsened.

Does DRO type matter?: Cycle versus resetting contingencies in eliminating responding.

Following lever-press training on variable-interval 30-s schedules, rats were exposed to three types of schedules designed to eliminate lever pressing. The first two were variations on what is called a differential-reinforcement-of-other-behavior (DRO, "zero rate", or [target response] omission schedule) schedule. Under both variations, reinforcers were scheduled to occur in different conditions after either fixed or variable inter-reinforcer intervals (IRIs). Under one variation each lever press reset the time interval (i.e., "resetting DRO") and under the other a reinforcer delivery scheduled at the end of an IRI was cancelled by the first response during the IRI (i.e., "cycle DRO"). In another condition reinforcers were delivered independently of responding after fixed or variable time periods. Each of the DRO procedures reduced response rates quickly and to near zero across ten sessions. The time schedules also reduced responding, albeit at a slower rate. The results extend the analogy of omission training to freeoperant avoidance to shock-deletion avoidance schedules.

Hierarchical resurgence.

In resurgence, conventionally a target response is trained and then extinguished while some alternative response is reinforced. In the most common procedure, when the latter is extinguished, the former resurges. The present experiments examined resurgence after two responses were trained sequentially and subsequently extinguished. In Experiments 1 and 2, keypecking to one key was trained and then extinguished as keypecking to a different key was trained then later extinguished. In both experiments, regardless of the spatial location of the different keys, the last-trained response resurged before the first-trained one. The results were replicated in Experiment 3 where reinforcement rate of the first-trained response was four times that of the second-trained response. The results in conjunction with earlier experiments suggest that resurgence occurs hierarchically, although whether more or less recently trained target responses resurge first or later may depend on both current and historical variables. The results also raise questions about the interpretation of responding on a control key that sometimes is included in resurgence experiments to isolate resurgence from extinction-induced responding.

Reinforcer magnitude and resurgence.

One experiment each was conducted with pigeons and rats to assess the effects of changes in reinforcer magnitude on resurgence. Each experiment involved three phases. In the Training phase, key pecking (Experiment 1) or lever pressing (Experiment 2) on two concurrently available operanda was reinforced according to variable-interval schedules. In the Alternative Reinforcement phase, responding to one operandum was extinguished while that to the other was reinforced with greater duration of food access (Experiment 1), greater number of pellets (Experiment 2a), or a similar number of pellets (Experiment 2b) than occurred in the Training phase. In the Resurgence Test phase, the reinforcer magnitude associated with the Alternative response was either reduced (Experiments 1 & 2a) or increased (Experiment 2b) relative to the preceding condition. Resurgence generally occurred when the reinforcer magnitude maintaining the Alternative response was reduced, but not when it was increased relative to the preceding condition. The results further support the suggestion that resurgence results from an overall "worsening" of reinforcement conditions, but not simply from a change in conditions.