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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

On defining resurgence.

A review of different investigators' definitions of resurgence revealed several common features: First, characteristics of the resurgent, or target, response, such as its transience; magnitude; time course within and across sessions; and relativity to a baseline response rate are not mentioned. Second, the target response is described as being established through its reinforcement in the first, or Training, phase of a resurgence procedure. Third, the target response must be eliminated as an alternative response is reinforced in the second, Alternative Reinforcement, phase of a resurgence procedure. Fourth, the alternative response must be extinguished during the Resurgence Test phase. Fifth, none of the definitions allude to any contribution of stimulus variables to resurgence. When reconsidered in light of contemporary research germane to these features, none of the reviewed definitions sufficiently reflect important variables in the generation and assessment of resurgence. The review concludes with a proposed working definition that takes into account contemporary research involving all of the aforementioned factors.

Analysis of the Prevalence of HTLV-1 Proviral DNA in Cervical Smears and Carcinomas from HIV Positive and Negative Kenyan Women.

The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some countries although its prevalence and relationship with other sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in genomic DNA extracted from liquid based cytology (LBC) cervical smears and invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus-positive (HIV+ve) and HIV-negative (HIV-ve) Kenyan women. Patient sociodemographic details were recorded by structured questionnaire and these data analysed with respect to HIV status, human papillomavirus (HPV) type (Papilocheck(®)) and cytology. This showed 22/113 (19.5%) of LBC's from HIV+ve patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV-ve women (p = 0.0002; odds ratio (OR) = 6.42 (2.07-26.56)). Only 1/37 (2.7%) of HIV+ve and none of the 44 HIV-ve ICC samples were positive for HTLV-1. There was also a significant correlation between HTLV-1 infection, numbers of sexual partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC samples was unexpected and the reasons for this are unclear.

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.

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease.

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC-ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874.

A survey of functional behavior assessment methods used by behavior analysts in practice.

To gather information about the functional behavior assessment (FBA) methods behavior analysts use in practice, we sent a web-based survey to 12,431 behavior analysts certified by the Behavior Analyst Certification Board. Ultimately, 724 surveys were returned, with the results suggesting that most respondents regularly use FBA methods, especially descriptive assessments. Moreover, the data suggest that the majority of students are being formally taught about the various FBA methods and that educators are emphasizing the range of FBA methods in their teaching. However, less than half of the respondents reported using functional analyses in practice, although many considered descriptive assessments and functional analyses to be the most useful FBA methods. Most respondents reported using informant and descriptive assessments more frequently than functional analyses, and a majority of respondents indicated that they "never" or "almost never" used functional analyses to identify the function of behavior.

High-sensitivity human papilloma virus genotyping reveals near universal positivity in anal squamous cell carcinoma: different implications for vaccine prevention and prognosis.

BACKGROUND: Characterisation of human papilloma virus (HPV) infection in anal squamous cell carcinoma (ASCC) may have dual importance: first, aetiological; second, prognostic, informing outcome after chemo-radiotherapy (CRT). We undertook HPV genotyping, and allelic characterisations, to evaluate the aetiological role of HPV while simultaneously evaluating the impact of HPV genotyping on relapse-free (RFS) and overall survival (OS). METHOD: Dual-primer HPV genotyping (subtypes 6, 11, 16, 18, 31, 33, 45, 52, 58) and DNA sequencing of HPV 16 positive tumours were analysed in 151 consecutively referred ASCCs, previously characterised by immunohistochemistry for p16 expression. In 110 patients treated with CRT, factors influencing RFS and OS were evaluated using univariate and multivariate models. RESULTS: HPV positivity was observed in 95%. HPV 16 accounted for 89%; of these, 64% harboured the T350G E6 variant. HPV 16 positivity was significantly correlated with improved 5-year RFS (62% versus 40%; p = 0.027) and OS (59% versus 38%; p = 0.019). p16 expression was also significantly correlated with improved 5-year RFS (positive versus negative: 65% versus 16%; p < 0.0001) and OS (63% versus 13%; p < 0.0001). In multivariable models that included HPV 16 status, p16 status, sex, and age, p16 expression remained an independent prognostic factor for RFS (p < 0.0001) and OS (p = 0.002). CONCLUSION: In ASCC, near-universal HPV detection rates were demonstrated, higher than generally reported in the literature, and supporting the development of multivalent HPV vaccinations for prevention. By contrast, p16 negatively, but not HPV 16 genotype, is an independent adverse prognosticator after chemo-radiotherapy in patients with ASCC.