Variation in the practice of wide local excision for melanoma in Ireland and the UK: a questionnaire survey.

BACKGROUND: Wide local excision (WLE) is standard practice in the management of melanoma, but no national or international guidelines exist regarding its technique. OBJECTIVES: To assess variation in the practice of WLE and to explore the effect of clinicians' specialty and grade on such variation. METHODS: This was an international, anonymized, cross-sectional study. An online questionnaire was distributed to the Irish Association of Dermatologists, British Association of Dermatologists, British Association of Plastic and Reconstructive and Aesthetic Surgeons, Melanoma Focus and BioGenoMEL members. RESULTS: Of 128 respondents, 57% were dermatologists and 38% plastic surgeons. Most (80%) were consultants. Almost all clinicians learned their technique from colleagues (99%) 'on the job', although 21% also used textbooks or other media as part of WLE training. There was significant variation in planning and performing WLE: 59% considered margins already achieved, 71% marked margins with the skin relaxed. For 1 cm WLE, 84% delineated 1 cm from the edge of the scar; with a greater proportion of plastic surgeons than dermatologists marking from the centre of the scar (P < 0.05). Most followed a longitudinal/oblique axis on the limbs for WLE (81%). Only 40% sent 'dog ears' for histology. Most (70%) incised through the marked line, 27% incised outside it. Most (79%) excised to deep fascia, 18% to the next biological margin. CONCLUSIONS: This study demonstrates significant variation among clinicians performing WLE, an essential component of melanoma management. We postulate that this could have an impact on patient outcomes. A consensus statement should be developed, to achieve more consistency in the practice of WLE.

Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study.

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age: 18-60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

How Much of Me Do I See in Other Minds? Modulating Egocentricity in Emotion Judgments by tDCS.

When inferring the mental states of others, individuals' judgments are influenced by their own state of mind, an effect often referred to as egocentricity. Self-other differentiation is key for an accurate interpretation of other's mental states, especially when these differ from one's own states. It has been suggested that the right supramarginal gyrus (rSMG) is causally involved in overcoming egocentricity in the affective domain. In a double-blind randomized study, 47 healthy adults received anodal (1 mA, 20 min) or sham transcranial direct current stimulation (tDCS) to the rSMG prior to performing a newly developed paradigm, the self-other facial emotion judgment (SOFE) task. In this task, participants made judgments of facial emotional expressions while having been previously confronted with congruent or incongruent emotion-inducing situations. To differentiate between emotional and cognitive egocentricity, participants additionally completed an established visual perspective-taking task. Our results confirmed the occurrence of emotional egocentric biases during the SOFE task. No conclusive evidence of a general role of the rSMG in emotional egocentricity was found. However, active as compared to sham tDCS induced descriptively lower egocentric biases when judging incongruent fearful faces, and stronger biases when judging incongruent happy faces, suggesting emotion-specific tDCS effects on egocentric biases. Further, we found significant tDCS effects on cognitive egocentricity. Results of the present study expanded our understanding of emotional egocentricity and point towards emotion-specific patterns of the underlying functionality.

Effluent decontamination by the ibuprofen-mineralizing strain, Sphingopyxis granuli RW412: Metabolic processes.

The high global consumption of ibuprofen and its limited elimination by wastewater treatment plants (WWTPs), has led to the contamination of aquatic systems by this common analgesic and its metabolites. The potentially negative environmental and public health effects of this emerging contaminant have raised concerns, driving the demand for treatment technologies. The implementation of bacteria which mineralize organic contaminants in biopurification systems used to decontaminate water or directly in processes in WWTPs, is a cheap and sustainable means for complete elimination before release into the environment. In this work, an ibuprofen-mineralizing bacterial strain isolated from sediments of the River Elbe was characterized and assayed to remediate different ibuprofen-polluted media. Strain RW412, which was identified as Sphingopyxis granuli, has a 4.48 Mb genome which includes plasmid sequences which harbor the ipf genes that encode the first steps of ibuprofen mineralization. Here, we confirm that these genes encode enzymes which initiate CoA ligation to ibuprofen, followed by aromatic ring activation by a dioxygenase and retroaldol cleavage to unequivocally produce 4-isobutylcatechol and propionyl-CoA which then undergo further degradation. In liquid mineral salts medium, the strain eliminated more than 2 mM ibuprofen within 74 h with a generation time of 16 h. Upon inoculation into biopurification systems, it eliminated repeated doses of ibuprofen within a few days. Furthermore, in these systems the presence of RW412 avoided the accumulation of ibuprofen metabolites. In ibuprofen-spiked effluent from a municipal WWTP, ibuprofen removal by this strain was 7 times faster than by the indigenous microbiota. These results suggest that this strain can persist and remain active under environmentally relevant conditions, and may be a useful innovation to eliminate this emerging contaminant from urban wastewater treatment systems.

Facial mimicry, empathy, and emotion recognition: a meta-analysis of correlations.

A number of prominent theories have linked tendencies to mimick others' facial movements to empathy and facial emotion recognition, but evidence for such links is uneven. We conducted a meta-analysis of correlations of facial mimicry with empathy and facial emotion recognition skills. Other factors were also examined for moderating influence, e.g. facets of empathy measured, facial muscles recorded, and facial emotions being mimicked. Summary effects were estimated with a random-effects model and a meta-regression analysis was used to identify factors moderating these effects. 162 effects from 28 studies were submitted. The summary effect size indicated a significant weak positive relationship between facial mimicry and empathy, but not facial emotion recognition. The moderator analysis revealed that stronger correlations between facial mimicry and empathy were observed for static vs. dynamic facial stimuli, and for implicit vs. explicit instances of facial emotion processing. No differences were seen between facial emotions, facial muscles, emotional and cognitive facets of empathy, or state and trait measures of empathy. The results support the claim that stronger facial mimicry responses are positively related to higher dispositions for empathy, but the weakness and variability of this effect suggest that this relationship is conditional on not-fully understood factors.

Neurobiological mechanisms of social cognition treatment in high-functioning adults with autism spectrum disorder.

BACKGROUND: The promise of precision medicine for autism spectrum disorder (ASD) hinges on developing neuroscience-informed individualized interventions. Taking an important step in this direction, we investigated neuroplasticity in response to an ecologically-valid, computer-based social-cognitive training (SCOTT). METHODS: In an active control group design, 48 adults with ASD were randomly assigned to a 3-month SCOTT or non-social computer training. Participants completed behavioral tasks, a functional and structural magnetic resonance imaging session before and after the training period. RESULTS: The SCOTT group showed social-cognitive improvements on close and distant generalization tasks. The improvements scaled with reductions in functional activity and increases in cortical thickness in prefrontal regions. CONCLUSION: In sum, we provide evidence for the sensitivity of neuroscientific methods to reflect training-induced social-cognitive improvements in adults with ASD. These results encourage the use of neuroimaging data to describe and quantify treatment-related changes more broadly.

Thinking about others and the future: Neural correlates of perspective taking relate to preferences for delayed rewards.

We infer the thoughts and feelings of others by taking their perspectives. Similar processes could be used to understand how we will be affected by future events, by allowing us to take the perspective of our future self. In this paper, we test this idea using a previously presented framework for guiding predictions. The framework proposes that a shared neural mechanism is involved in controlling egocentric bias, both while shifting our perspective away from self and towards others, and while shifting our perspective from immediate to future perspectives. To test this framework, 36 adults performed an intertemporal choice task. They were then scanned using 3T functional magnetic resonance imaging while completing a false-belief "localizer" task, which requires egocentric bias control. A positive correlation was observed between the right temporoparietal junction (rTPJ) response during the false-belief task, and preferences for delayed rewards in intertemporal choices. A subset of participants performed the intertemporal choice task again in the scanner, which revealed that the response of the same rTPJ cluster, individually localized during the false-belief task, was higher during delayed over immediate reward choices. In addition, functional connectivity between the rTPJ and ventromedial prefrontal cortex was found to differ between immediate and delayed choices. The current results indicate an overlap in processes of egocentric bias control and those that determine preferences in intertemporal choices, offering a social cognitive explanation for why rewards are devalued with delay in temporal discounting.

Does Intraindividual Variability of Personality States Improve Perspective Taking? An Ecological Approach Integrating Personality and Social Cognition.

Research integrating cognitive abilities and personality has focused on the role of personality traits. We propose a theory on the role of intraindividual variability of personality states (hereafter state variability) on perspective taking, in particular, the ability to infer other peoples' mental states. First, we review the relevant research on personality psychology and social cognition. Second, we propose two complementary routes by which state variability relates to anchoring and adjustment in perspective taking. The first route, termed ego-dispersion, suggests that an increased state variability decreases egocentric bias, which reduces anchoring. The second route, termed perspective-pooling, suggests that an increased state variability facilitates efficient adjustment. We also discuss how our theory can be investigated empirically. The theory is rooted in an ecological interpretation of personality and social cognition, and flags new ways for integrating these fields of research.

Amnesic patients show superior generalization in category learning.

OBJECTIVE: Generalization is the application of existing knowledge to novel situations. Questions remain about the precise role of the hippocampus in this facet of learning, but a connectionist model by Gluck and Myers (1993) predicts that generalization should be enhanced following hippocampal damage. METHOD: In a two-category learning task, a group of amnesic patients (n = 9) learned the training items to a similar level of accuracy as matched controls (n = 9). Both groups then classified new items at various levels of distortion. RESULTS: The amnesic group showed significantly more accurate generalization to high-distortion novel items, a difference also present compared to a larger group of unmatched controls (n = 33). CONCLUSIONS: The model prediction of a broadening of generalization gradients in amnesia, at least for items near category boundaries, was supported by the results. Our study shows for the first time that amnesia can sometimes improve generalization. (PsycINFO Database Record

The role of simulation in intertemporal choices.

One route to understanding the thoughts and feelings of others is by mentally putting one's self in their shoes and seeing the world from their perspective, i.e., by simulation. Simulation is potentially used not only for inferring how others feel, but also for predicting how we ourselves will feel in the future. For instance, one might judge the worth of a future reward by simulating how much it will eventually be enjoyed. In intertemporal choices between smaller immediate and larger delayed rewards, it is observed that as the length of delay increases, delayed rewards lose subjective value; a phenomenon known as temporal discounting. In this article, we develop a theoretical framework for the proposition that simulation mechanisms involved in empathizing with others also underlie intertemporal choices. This framework yields a testable psychological account of temporal discounting based on simulation. Such an account, if experimentally validated, could have important implications for how simulation mechanisms are investigated, and makes predictions about special populations characterized by putative deficits in simulating others.

Autistic traits modulate mimicry of social but not nonsocial rewards.

Autism Spectrum Conditions (ASC) are associated with diminished responsiveness to social stimuli, and especially to social rewards such as smiles. Atypical responsiveness to social rewards, which reinforce socially appropriate behavior in children, can potentially lead to a cascade of deficits in social behavior. Individuals with ASC often show diminished spontaneous mimicry of social stimuli in a natural setting. In the general population, mimicry is modulated both by the reward value and the sociality of the stimulus (i.e., whether the stimulus is perceived to belong to a conspecific or an inanimate object). Since empathy and autistic traits are distributed continuously in the general population, this study aimed to test if and how these traits modulated automatic mimicry of rewarded social and nonsocial stimuli. High and low rewards were associated with human and robot hands using a conditioned learning paradigm. Thirty-six participants from the general population then completed a mimicry task involving performing a prespecified hand movement which was either compatible or incompatible with a hand movement presented to the participant. High autistic traits (measured using the Autism Spectrum Quotient, AQ) predicted lesser mimicry of high-reward than low-reward conditioned human hands, whereas trait empathy showed an opposite pattern of correlations. No such relations were observed for high-reward vs. low-reward conditioned robot hands. These results demonstrate how autistic traits and empathy modulate the effects of reward on mimicry of social compared to nonsocial stimuli. This evidence suggests a potential role for the reward system in underlying the atypical social behavior in individuals with ASC, who constitute the extreme end of the spectrum of autistic traits.

The role of empathy in choosing rewards from another's perspective.

As social animals, we regularly act in the interest of others by making decisions on their behalf. These decisions can take the form of choices between smaller short-term rewards and larger long-term rewards, and can be effectively indexed by temporal discounting (TD). In a TD paradigm, a reward loses subjective value with increasing delay presumably because it becomes more difficult to simulate how much the recipient (e.g., future self) will value it. If this is the case, then the value of delayed rewards should be discounted even more steeply when we are choosing for someone whose feelings we do not readily simulate, such as socially distant strangers. Second, the ability to simulate shows individual differences and is indexed by trait empathy. We hypothesized that individuals high in trait empathy will more readily simulate, and hence discount less steeply for distant others, compared to those who are low on trait empathy. To test these predictions, we asked 63 participants from the general population to perform a TD task from the perspectives of close and distant others, as well as their own. People were found to discount less steeply for themselves, and the steepness of TD increased with increasing distance from self. Additionally, individuals who scored high in trait empathy were found to discount less steeply for distant others compared to those who scored low. These findings confirm the role of empathy in determining how we choose rewards for others.

"Can it read my mind?" - What do the public and experts think of the current (mis)uses of neuroimaging?

Emerging applications of neuroimaging outside medicine and science have received intense public exposure through the media. Media misrepresentations can create a gulf between public and scientific understanding of the capabilities of neuroimaging and raise false expectations. To determine the extent of this effect and determine public opinions on acceptable uses and the need for regulation, we designed an electronic survey to obtain anonymous opinions from as wide a range of members of the public and neuroimaging experts as possible. The surveys ran from 1(st) June to 30 September 2010, asked 10 and 21 questions, respectively, about uses of neuroimaging outside traditional medical diagnosis, data storage, science communication and potential methods of regulation. We analysed the responses using descriptive statistics; 660 individuals responded to the public and 303 individuals responded to the expert survey. We found evidence of public skepticism about the use of neuroimaging for applications such as lie detection or to determine consumer preferences and considerable disquiet about use by employers or government and about how their data would be stored and used. While also somewhat skeptical about new applications of neuroimaging, experts grossly underestimated how often neuroimaging had been used as evidence in court. Although both the public and the experts rated highly the importance of a better informed public in limiting the inappropriate uses to which neuroimaging might be put, opinions differed on the need for, and mechanism of, actual regulation. Neuroscientists recognized the risks of inaccurate reporting of neuroimaging capabilities in the media but showed little motivation to engage with the public. The present study also emphasizes the need for better frameworks for scientific engagement with media and public education.

Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals.

Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs.

Schizophrenia risk genes: Implications for future drug development and discovery.

Present-day development of improved treatments for schizophrenia is hindered by uncertain models of disease, inter-individual response variability in clinical trials and a paucity of sensitive measures of treatment effects. Findings from genetic research emphasize the potential for schizophrenia risk genes to help develop focused treatments, discover new drug targets and provide markers of clinical subtypes. Advances in genetic technologies also provide novel modes of drug discovery in schizophrenia such as transcriptomics, epigenetics and transgenic animal models. In this review, we discuss proven and proposed ways risk genes can be used to enhance the development and discovery of treatments for schizophrenia and highlight key studies in these approaches.