Developing the Function Acquisition Speed Test: Using a Functional Research Approach to Build a Novel Implicit Test

The eleven studies reported in this thesis outline the development of a novel implicit test for assessing verbal and social histories. This measure was named the “Function Acquisition Speed Test” (FAST). The current research utilizes a functional research approach drawing upon the seminal research by Watt, Keenan, Barnes and Cairns (1991) and upon more recent research by Gavin, Roche and Ruiz (2008) to inform the bottom-up development of the FAST. Chapter 1 presents a review the behaviour analytic literature concerned with the phenomena of stimulus equivalence and derived relational responding, and reviews the links between these concepts and complex human behaviour such as attitudes. The seminal study by Watt et al. (1991) is also described. In that study, the researchers attempted to train subjects to form two equivalence classes which were incongruent with Northern Irish subjects’ socioverbal history (i.e. containing Catholic names and Protestant symbols) using a stimulus equivalence paradigm. Watt et al. concluded that pre-existing social histories can interfere with the acquisition of novel stimulus relations. The relevance of this work as an underpinning principle of the FAST is described. Chapter 1 also briefly reviews the social cognitive approach to implicit testing and discusses the value of a functional approach. Also in Chapter 1, the initial structure of the FAST paradigm is outlined. The key FAST test blocks present subjects with one stimulus per trial, and require subjects to learn to emit one of two responses (i.e. press right or press left) based on corrective feedback. In the consistent block, the same response is required for the two stimuli suspected to be related, while the other response is required for two novel, unrelated stimuli. In the inconsistent block, the two stimuli of interest require two different responses. The reinforcement contingencies of the inconsistent act as a behavioural disrupter, and the difference in learning rates between the two blocks is taken to be indicative of the strength of the relation between the test stimuli. Chapter 2 reports on five experiments that tested the underlying premise of the FAST with regard to experimentally trained stimulus relations. In each of the experiments in this chapter, subjects completed training procedures to establish a stimulus relation which would later be probed for using the FAST methodology. In Experiment 1, subjects completed matching to sample training which established a simple A-B relation between two three-letter nonsense syllables. The FAST was capable of detecting the trained relations in a majority of subjects and on a group level, thus establishing a basic proof of concept for the methodology. Experiment 2 sought to expand on this by establishing aversive or erotic stimulus functions for a pair of nonsense syllables. The FAST procedure was then used to test for a relation between a nonsense syllable and related (but novel) romantic images. The FAST was also run multiple times for each subject. The results revealed a great deal of instability over time, with the expected effect only emerging on the second of three FAST runs. In Experiment 3, subjects were trained using a Matching-to-Sample procedure to create two three-member equivalence classes. The derived relations (A1-C1) were then tested for using the FAST. Given the importance of derived relational responding to a behavioural account of attitudes, this was a vital test for the fledgling format. The FAST was successful in detecting the derived relations, and this effect emerged on all three runs of the FAST. Experiment 4 sought to further build on this success by utilising an extremely robust and extended training procedure to maximise the probability of the emergence of stable equivalence relations. The training procedure contained nine stages of increasing difficulty and fading of consequences. A repeated single subjects design was used, and 4 out of five subjects showed strong positive FAST effects when tested. Experiment 5 investigated the question of whether the FAST was capable of detecting the influence of derived relations which had not yet been tested for by a normal equivalence testing procedure. All subjects completed an equivalence training procedure, but half of the experimental subjects completed a FAST prior to completing an equivalence test, while the other half completed a FAST after completing a normal equivalence test. The FAST was unable to detect the derived relations in the former experimental group, even in subjects who latter passed the equivalence test. The implications of this result for a Relational Frame Theory account of implicit attitudes are discussed. In Chapter 3, the effect of a number of basic procedural modifications to the FAST presentation was considered. In each experiment, subjects completed 3 successive runs of a FAST after having been trained in a simple A-B stimulus relation. Experiment 6 used a between subjects design to measure the effect of varied response windows on FAST performance (1000ms, 2000ms, 3000ms or 4000ms). Experiment 7 investigated the effect of including a variable number of practice blocks prior to the first baseline block (3, 5, or 7 practice blocks). Experiment 8 varied the fluency criterion for completing a FAST block. (7, 8, or 9 correct in a sequence of ten responses.). The results of these experiments were difficult to interpret due to instability in the predicted FAST effect across the three runs of the FAST. Possible reasons for this instability are discussed, and improvements to the FAST are suggested. The results of these experiments resulted in a shortening of the FAST response window to 2000ms, the inclusion of a practice block, and the inclusion of a “counter” which displayed the number of correct responses in a row that the subject had emitted. Chapter 4 tested the FAST with “real world” stimuli as the test stimuli. In each experiment in Chapter 4, subjects complete FAST procedures aimed at detecting natural histories of verbal behaviour. In each experiment, a different relation is targeted. In experiment 9, the FAST probes for a relation between the words “spider” and “disgust”. Experiment 10 targets the relations “immigrant” and “cheat”. Experiment 11 departs from using words as stimuli, using images of teenaged females to probe for relations between sexual images and images of teenaged females of different ages. The results of these experiments demonstrate both the limitations and strengths of the FAST procedure in different contexts. The FAST was shown to be most capable of detecting culturally ubiquitous verbal relations (spiders are disgusting); particularly in cases where the two stimuli are strongly in opposition (i.e. young girls are sexual). Experiment 11 also demonstrated the potential of the FAST to be deployed in serial to examine the “shape” of an equivalence class. Subjects in experiment 11 showed a strong negative FAST effect when female stimuli were pre-teenaged, but this effect quickly vanished as the ages of the pictured females increased into the teenage years. Chapter 5 provides an overview of the entire research project. The experimental findings from each of the previous chapters are discussed along with the implications of these findings. The early development of this novel test format is charted, and remaining challenges that must be confronted in future research are outlined. Alternative experimental preparations emerging from this research are also considered and explored, and possible applications in both basic research and applied setting are discussed

A new generation of smart amine donors for transaminase-mediated biotransformations

The application of ω-transaminase biocatalysts for the synthesis of optically pure chiral amines presents a number of challenges, including difficulties associated with displacing the challenging reaction equilibria. Herein, we report a highly effective approach using low equivalents of the novel diamine donor, cadaverine, which enables high conversions of challenging substrates to the corresponding chiral amines in excellent ee. This approach paves the way for the design of self-sufficient fermentation processes combining transaminase biotransformations with existing strategies for cadaverine production via decarboxylation of endogenous lysine

A Function Acquisition Speed Test for Equivalence Relations.

The current study employed a stimulus equivalence paradigm to assess the ability of the recently developed Function Acquisition Speed Test (FAST) to measure the existence and strength of experimentally produced derived relations. Twenty-two participants were exposed to a One-to-Many stimulus equivalence training procedure (A1–B1, A1–C1, A2–B2, A2–C2), followed by testing for derived B1–C1 and B2–C2 relations. All participants were then exposed to a FAST procedure in which a simple common operant response was established for pairs of equivalent stimuli (e.g., B1 and C1) in one block of training. In another bock of training, a common response was established for pairs of non-equivalent stimuli (e.g., B1 and C2). Trial numbers required for participants to reach mastery criteria differed across the two FAST blocks, as expected, but only for those participants who had passed the prior equivalence testing phase. This finding suggest that the FAST procedure functions as both a concurrent measure of stimulus equivalence class emergence and a functional-analytic tool that might assess unreinforced and socially sensitive stimulus relations formed in the world outside the laboratory. Large inter- and intra-participant variations in performances across FAST blocks are discussed

Core functionalization of semi-crystalline polymeric cylindrical nanoparticles using photo-initiated thiol–ene radical reactions

Sequential ring-opening and reversible addition–fragmentation chain transfer (RAFT) polymerization was used to form a triblock copolymer of tetrahydropyran acrylate (THPA), 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) and L-lactide. Concurrent deprotection of the THPA block and crystallization-driven self-assembly (CDSA) was undertaken and allowed for the formation of cylindrical micelles bearing allyl handles in a short outer core segment. These handles were further functionalized by different thiols using photo-initiated thiol–ene radical reactions to demonstrate that the incorporation of an amorphous PMAC block within the core does not disrupt CDSA and can be used to load the cylindrical nanoparticles with cargo

Sterol 3β-glucosyltransferase biocatalysts with a range of selectivities, including selectivity for testosterone

The main objectives of this work were to characterise a range of purified recombinant sterol 3β-glucosyltransferases and show that rational sampling of the diversity that exists within sterol 3β-glucosyltransferase sequence space can result in a range of enzyme selectivities. In our study the catalytically active domain of the Saccharomyces cerevisiae 3β-glucosyltransferase was used to mine putative sterol 3β-glucosyltransferases from the databases. Selected diverse sequences were expressed in and purified from Escherichia coli and shown to have different selectivities for the 3β-hydroxysteroids ergosterol and cholesterol. Surprisingly, three enzymes were also selective for testosterone, a 17β-hydroxysteroid. This study therefore reports for the first time sterol 3β-glucosyltransferases with selectivity for both 3β- and 17β-hydroxysteroids and is also the first report of recombinant 3β-glucosyltransferases with selectivity for steroids with a hydroxyl group at positions other than C-3. These enzymes could therefore find utility in the pharmaceutical industry for the green synthesis of a range of glycosylated compounds of medicinal interest

Safety of trastuzumab (Herceptin®) during pregnancy: two case reports

We report on two cases of women on trastuzumab therapy for breast cancer who became pregnant and delivered healthy live infants. At the time of reporting the children are growing and developing normally (ages 3 and 2)

Is threat in the way they move? Influences of static and gait information on threat judgments of unknown people

Recognising intraspecies threat is essential for survival. However, this needs to be balanced against the undue avoidance of unknown others who may be useful to us. Research has shown that judgments of ‘aggression’ and ‘threat’ posed by an unknown person can accurately reflect that person’s general aggressive tendencies. To date, there has not been a within-sample comparison of the informativeness of static and walking stimuli for threat judgments. In this study, 193 participants rated the threat posed by 23 target people presented as both simplified gait presentations (point-light walkers) and still images. We analysed how threat judgments made by participants were predicted by the target’s self-reported aggression (accuracy), the sex of the targets and the medium of target presentation (point-light vs. still image). Our results showed that participants’ threat judgments accurately predicted targets’ aggression. Male targets received higher threat ratings than female targets and point-light displays were rated as more threatening than still images. There were no effects of target sex and presentation medium on accuracy of threat perception and no sex by medium interactions on judgments themselves. Overall, this study provides further evidence of the accuracy of threat judgments at detecting trait aggression. However, further research is needed to explain what features of the target people are enabling the accurate judgments of aggression

LC3B globular structures correlate with survival in esophageal adenocarcinoma

Background: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome. Previous studies have indicated that induction of autophagy can influence various aspects of tumor cell biology, including chemosensitivity. The objective of this study was to assess whether expression of the autophagy marker (LC3B) correlated with patient outcome. Methods: Esophageal adenocarcinoma tumor tissue from two independent sites, was examined retrospectively. Tumors from 104 neoadjuvant naïve patients and 48 patients post neoadjuvant therapy were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess impact of LC3B expression on survival. Cox regression was used to examine association with clinical risk factors. Results: A distinct globular pattern of LC3B expression was found to be predictive of outcome in both patient groups, irrespective of treatment (p < 0.001). Multivariate analysis found that this was a strong independent predictor of poor prognosis (p < 0.001). Conclusions: This distinctive staining pattern of LC3B represents a novel prognostic marker for resectable esophageal adenocarcinoma