Health professional and patient views of a novel prognostic test for melanoma: A theoretically informed qualitative study.

OBJECTIVES: Cutaneous melanoma rates are steadily increasing. Up to 20% of patients diagnosed with AJCC Stage I/II melanomas will develop metastatic disease. To date there are no consistently reliable means to accurately identify truly high versus low-risk patient subpopulations. There is hence an urgent need for more accurate prediction of prognosis to determine appropriate clinical management. Validation of a novel prognostic test based on the immunohistochemical expression of two protein biomarkers in the epidermal microenvironment of primary melanomas was undertaken; loss of these biomarkers had previously been shown to be associated with a higher risk of recurrence or metastasis. A parallel qualitative study exploring secondary care health professional and patient views of the test was undertaken and this paper reports the perceived barriers and enablers to its implementation into the melanoma care pathway. METHODS: Qualitative methods were employed drawing upon the Theoretical Domains Framework (TDF) in the exploration and analysis. An inductive-deductive analysis was performed, with all data coded using a thematic then TDF framework. FINDINGS: 20 dermatologists, plastic surgeons, cancer nurse specialists, oncologists and histopathologists participated. Nine TDF domains were relevant to all health professional groups and the 'Skills' and 'Beliefs about Capabilities' domains were relevant only to histopathologists. 'Optimism' and 'Beliefs about consequences' were strong enablers particularly for clinicians. 'Environmental context and resources' (impact on pathology services) and 'Knowledge' (the need for robust evidence about the test reliability) were the main perceived barriers. 19 patients and one carer were interviewed. For the patients eight domains were relevant. ('Knowledge', 'Emotions', 'Beliefs about consequences', 'Social Role and identity', 'Behavioural regulation', 'Memory, attention and decision processes', 'Reinforcement' and 'Skills'). The consequences of the implementation of the test were reassurance about future risk, changes to the follow-up pathway on which there were mixed views, and the need to ensure they maintained self-surveillance (Beliefs about consequences). The test was acceptable to all patient interviewees but the resultant changes to management would need to be supported by mechanisms for fast-track back into the clinic, further information on self-surveillance and clear management plans at the time the result is conveyed (Behavioural regulation). CONCLUSIONS: Health professionals and patients perceived positive consequences-for patients and for health services-of adopting the test. However, its implementation would require exploration of the resource implications for pathology services, psychological support for patients with a high-risk test result and mechanisms to reassure and support patients should the test lead to reduced frequency or duration of follow-up. Exploring implementation at an early stage with health professionals presented challenges related to the provision of specific details of the test and its validation.

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1.

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC.Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC).

The Sound of Grasp Affordances: Influence of Grasp-Related Size of Categorized Objects on Vocalization.

Previous research shows that simultaneously executed grasp and vocalization responses are faster when the precision grip is performed with the vowel [i] and the power grip is performed with the vowel [ɑ]. Research also shows that observing an object that is graspable with a precision or power grip can activate the grip congruent with the object. Given the connection between vowel articulation and grasping, this study explores whether grasp-related size of observed objects can influence not only grasp responses but also vowel pronunciation. The participants had to categorize small and large objects into natural and manufactured categories by pronouncing the vowel [i] or [ɑ]. As predicted, [i] was produced faster when the object's grasp-related size was congruent with the precision grip while [ɑ] was produced faster when the size was congruent with the power grip (Experiment 1). The effect was not, however, observed when the participants were presented with large objects that are not typically grasped by the power grip (Experiment 2). This study demonstrates that vowel production is systematically influenced by grasp-related size of a viewed object, supporting the account that sensory-motor processes related to grasp planning and representing grasp-related properties of viewed objects interact with articulation processes. The paper discusses these findings in the context of size-sound symbolism, suggesting that mechanisms that transform size-grasp affordances into corresponding grasp- and articulation-related motor programs might provide a neural basis for size-sound phenomena that links small objects with closed-front vowels and large objects with open-back vowels.

Heritage and Stigma. Co-producing and communicating the histories of mental health and learning disability.

University engagement with mental health services has traditionally been informed by the vocational and pedagogical links between the two sectors. However, a growth in the interest in public history and in the history of mental healthcare has offered new opportunities for those in the humanities to engage new audiences and to challenge perceptions about care in the past. The introduction of the 'impact agenda' and related funding streams has further encouraged academics to contribute to historical debates, and to those concerning current services. One such example of this is the Arts and Humanities Research Council funded Heritage and Stigma project at the University of Huddersfield, which was conceived to support mental health and learning disability charities in the exploration and dissemination of their own histories. Using this project as a case study, this paper will draw on primary source material to reflect on the opportunities and challenges of working in partnership with such groups. In particular, it will consider the need to address issues of stigma and exclusion in tandem with a critical understanding of the moves to 'community care' instigated by landmark legislation in the form of the 1959 Mental Health Act. Overall, it provides evidence of an inclusive, coproductive model of design and highlights the positive contribution to communicating mental health made by those based in the humanities.

Ocular drift along the mental number line.

We examined the spontaneous association between numbers and space by documenting attention deployment and the time course of associated spatial-numerical mapping with and without overt oculomotor responses. In Experiment 1, participants maintained central fixation while listening to number names. In Experiment 2, they made horizontal target-direct saccades following auditory number presentation. In both experiments, we continuously measured spontaneous ocular drift in horizontal space during and after number presentation. Experiment 2 also measured visual-probe-directed saccades following number presentation. Reliable ocular drift congruent with a horizontal mental number line emerged during and after number presentation in both experiments. Our results provide new evidence for the implicit and automatic nature of the oculomotor resonance effect associated with the horizontal spatial-numerical mapping mechanism.

I see what you say: Prior knowledge of other's goals automatically biases the perception of their actions.

We investigated whether top-down expectations about an actor's intentions affect action perception in a representational momentum (RM) paradigm. Participants heard an actor declare an intention to either take or leave an object and then saw him either reach for or withdraw from it, such that action and intention were either congruent or incongruent. Observers generally misperceived the hand's disappearance point further along the trajectory than it actually was, in line with the idea that action perception incorporates predictions of the action's future course. Importantly, this RM effect was larger for actions congruent with the actor's goals than for incongruent actions. These results demonstrate that action prediction integrates both current motion and top-down knowledge about the actor's intention. They support recent theories that emphasise the role of prior expectancies and prediction errors in social (and non-social) cognitive processing.

One step ahead: The perceived kinematics of others' actions are biased toward expected goals.

Action observation is often conceptualized in a bottom-up manner, where sensory information activates conceptual (or motor) representations. In contrast, here we show that expectations about an actor's goal have a top-down predictive effect on action perception, biasing it toward these goals. In 3 experiments, participants observed hands reach for or withdraw from objects and judged whether a probe stimulus corresponded to the hand's final position. Before action onset, participants generated action expectations on the basis of either object types (safe or painful, Experiments 1 and 2) or abstract color cues (Experiment 3). Participants more readily mistook probes displaced in a predicted position (relative to unpredicted positions) for the hand's final position, and this predictive bias was larger when the movement and expectation were aligned. These effects were evident for low-level movement and high-level goal expectancies. Expectations bias action observation toward the predicted goals. These results challenge current bottom-up views and support recent predictive models of action observation.

The oculomotor resonance effect in spatial-numerical mapping.

We investigated automatic Spatial-Numerical Association of Response Codes (SNARC) effect in auditory number processing. Two experiments continually measured spatial characteristics of ocular drift at central fixation during and after auditory number presentation. Consistent with the notion of a spatially oriented mental number line, we found spontaneous magnitude-dependent gaze adjustments, both with and without a concurrent saccadic task. This fixation adjustment (1) had a small-number/left-lateralized bias and (2) it was biphasic as it emerged for a short time around the point of lexical access and it received later robust representation around following number onset. This pattern suggests a two-step mechanism of sensorimotor mapping between numbers and space - a first-pass bottom-up activation followed by a top-down and more robust horizontal SNARC. Our results inform theories of number processing as well as simulation-based approaches to cognition by identifying the characteristics of an oculomotor resonance phenomenon.

'Without decontextualisation': the Stanley Royd Museum and the progressive history of mental health care.

This paper builds on recent scholarship exploring museum exhibitions and the heritage of mental health care. Using the development of the Stanley Royd Museum in the mid-1970s as a case study, the paper will examine the rationale for the opening of the museum and its link to changing perceptions of mental hospitals in both historical study and what was then 'current' practice. It will then provide an overview of the proposed audience for the new museum and briefly analyse its success in communicating its history to its visitors. Ultimately, it will question how successful mental health professionals were in presenting the progressive nature of institutional care at a time when the system was being radically overhauled and reoriented.

I don't get you. Action observation effects inverted by kinematic variation.

Recent studies have reported an intricate interplay between affordance and mirror effects (the imitation of another agent) when participants attend to the concurrent presentation of an object and another agent interacting with it. In the present paper, we compare two experimental settings in which an observed action was presented as a prime for a task involving the categorization of a graspable object. In experiment 1a, the action depicted a reach and grasp gesture whereas in experiment 1b, only the reach phase was presented. This modification led to very different outcomes. Experiment 1a reflected the traditional imitation effect elicited by human motion. Conversely, experiment 1b showed the facilitation of contralateral responses. Affordance effects were found in experiment 1a only for the RVF. Our results support the view that motor simulation processes underlying imitation or joint actions are extremely sensitive to specific phase kinematics.

Planning-related motor processes underlie mental practice and imitation learning.

It is still controversial whether mental practice-the internal rehearsal of movements to improve later performance-relies on processes engaged during physical motor performance and, if so, which processes these are. We report data from 5 experiments, in which participants mentally practiced complex rhythms with either feet or hands while using the same or different body parts to respond to unrelated sounds. We found that responses were impaired for those body parts that were concurrently used in mental practice, suggesting a binding of body-part-specific motor processes to action plans. This result was found when participants mentally trained to memorize the rhythms, to merely improve their performance, when mental practice and execution directly followed one another and when separated by a different task. Finally, it was found irrespective of whether participants practiced on the basis of a symbolic rhythm description and when they practiced by watching somebody perform the rhythms (imitation learning). The effect was eliminated only when the requirement for mental practice was eliminated from the task while keeping visual stimulation identical. These data link mental practice not to execution but planning related motor processes and reveal that these planning processes underlie both mental practice and imitation learning.

Visual and linguistic cues to graspable objects.

Two experiments investigated (1) how activation of manual affordances is triggered by visual and linguistic cues to manipulable objects and (2) whether graspable object parts play a special role in this process. Participants pressed a key to categorize manipulable target objects copresented with manipulable distractor objects on a computer screen. Three factors were varied in Experiment 1: (1) the target's and (2) the distractor's handles' orientation congruency with the lateral manual response and (3) the Visual Focus on one of the objects. In Experiment 2, a linguistic cue factor was added to these three factors-participants heard the name of one of the two objects prior to the target display onset. Analysis of participants' motor and oculomotor behaviour confirmed that perceptual and linguistic cues potentiated activation of grasp affordances. Both target- and distractor-related affordance effects were modulated by the presence of visual and linguistic cues. However, a differential visual attention mechanism subserved activation of compatibility effects associated with target and distractor objects. We also registered an independent implicit attention attraction effect from objects' handles, suggesting that graspable parts automatically attract attention during object viewing. This effect was further amplified by visual but not linguistic cues, thus providing initial evidence for a recent hypothesis about differential roles of visual and linguistic information in potentiating stable and variable affordances (Borghi in Language and action in cognitive neuroscience. Psychology Press, London, 2012).

How affordances associated with a distractor object affect compatibility effects: a study with the computational model TRoPICALS.

Seeing an object activates both visual and action codes in the brain. Crucial evidence supporting this view is the observation of object to response compatibility effects: perception of an object can facilitate or interfere with the execution of an action (e.g., grasping) even when the viewer has no intention of interacting with the object. TRoPICALS is a computational model that proposes some general principles about the brain mechanisms underlying compatibility effects, in particular the idea that top-down bias from prefrontal cortex, and whether it conflicts or not with the actions afforded by an object, plays a key role in such phenomena. Experiments on compatibility effects using a target and a distractor object show the usual positive compatibility effect of the target, but also an interesting negative compatibility effect of the distractor: responding with a grip compatible with the distractor size produces slower reaction times than the incompatible case. Here, we present an enhanced version of TRoPICALS that reproduces and explains these new results. This explanation is based on the idea that the prefrontal cortex plays a double role in its top-down guidance of action selection producing: (a) a positive bias in favour of the action requested by the experimental task; (b) a negative bias directed to inhibiting the action evoked by the distractor. The model also provides testable predictions on the possible consequences of damage to volitional circuits such as in Parkinsonian patients.

Bodies and other visual objects: the dialectics of reaching toward objects.

Participants viewed video clips of a left or right-handed reach toward an object that was orientated with a handle to the left or right. They were required to classify the object by making a left or right-handed key-press and ignore the reach. These responses were, never-the-less, affected by the observed reach in ways which largely reflected the opportunities for complementary actions in the viewed scenes, given the simultaneous constraints of the object orientation combined with the direction and hand of reach. These influences are claimed to reflect the interdependency of the action possibilities that arise from a set of objects and agents in three-dimensional space that together determine behaviour.

Object affordance influences instruction span.

We measured memory span for assembly instructions involving objects with handles oriented to the left or right side. Right-handed participants remembered more instructions when objects' handles were spatially congruent with the hand used in forthcoming assembly actions. No such affordance-based memory benefit was found for left-handed participants. These results are discussed in terms of motor simulation as an embodied rehearsal mechanism.

Electrophysiological examination of embodiment in vision and action.

A wealth of behavioral data has shown that the visual properties of objects automatically potentiate motor actions linked with them, but how deeply are these affordances embedded in visual processing? In the study reported here, we used electrophysiological measures to examine the time course of affordance resulting from the leftward or rightward orientation of the handles of common objects. Participants were asked to categorize those objects using a left- or right-handed motor response. Lateralized readiness potentials showed rapid motor preparation in the hand congruent with the affordance provided by the object only 100 to 200 ms after stimulus presentation and up to 400 ms before the actual response. Examination of event-related potentials also revealed an effect of handle orientation and response-hand congruency on the visual P1 and N1 components. Both of these results suggest that activity in the early sensory pathways is modulated by the action associations of objects and the intentions of the viewer.

Attention deployment during memorizing and executing complex instructions.

We investigated the mental rehearsal of complex action instructions by recording spontaneous eye movements of healthy adults as they looked at objects on a monitor. Participants heard consecutive instructions, each of the form "move [object] to [location]". Instructions were only to be executed after a go signal, by manipulating all objects successively with a mouse. Participants re-inspected previously mentioned objects already while listening to further instructions. This rehearsal behavior broke down after 4 instructions, coincident with participants' instruction span, as determined from subsequent execution accuracy. These results suggest that spontaneous eye movements while listening to instructions predict their successful execution.

When motor attention improves selective attention: the dissociating role of saliency.

There is evidence that preparing and maintaining a motor plan ("motor attention") can bias visual selective attention. For example, a motor attended grasp biases visual attention to select appropriately graspable object features (Symes, Tucker, Ellis, Vainio, & Ottoboni, 2008). According to the biased competition model of selective attention, the relative weightings of stimulus-driven and goal-directed factors determine selection. The current study investigated how the goal-directed bias of motor attention might operate when the stimulus-driven salience of the target was varied. Using a change detection task, two almost identical photographed scenes of simplistic graspable objects were presented flickering back and forth. The target object changed visually, and this change was either high or low salience. Target salience determined whether or not the motor attended grasp significantly biased visual selective attention. Specifically, motor attention only had a reliable influence on target detection times when the visual salience of the target was low.

Grasp preparation improves change detection for congruent objects.

A series of experiments provided converging support for the hypothesis that action preparation biases selective attention to action-congruent object features. When visual transients are masked in so-called change-blindness scenes, viewers are blind to substantial changes between 2 otherwise identical pictures that flick back and forth. The authors report data in which participants planned a grasp prior to the onset of a change-blindness scene in which 1 of 12 objects changed identity. Change blindness was substantially reduced for grasp-congruent objects (e.g., planning a whole-hand grasp reduced change blindness to a changing apple). A series of follow-up experiments ruled out an alternative explanation that this reduction had resulted from a labeling or strategizing of responses and provided converging support that the effect genuinely arose from grasp planning.

On the relations between action planning, object identification, and motor representations of observed actions and objects.

Recent evidence suggests that viewing a static prime object (a hand grasp), can activate action representations that affect the subsequent identification of graspable target objects. The present study explored whether stronger effects on target object identification would occur when the prime object (a hand grasp) was made more action-rich and dynamic. Of additional interest was whether this type of action prime would affect the generation of motor activity normally elicited by the target object. Three experiments demonstrated that grasp observation improved the identification of grasp-congruent target objects relative to grasp-incongruent target objects. We argue from this data that identifying a graspable object includes the processing of its action-related attributes. In addition, grasp observation was shown to influence the motor activity elicited by the target object, demonstrating interplay between action-based and object-based motor coding.