Predictive Genetic Testing in Children: Constitutional Mismatch Repair Deficiency Cancer Predisposing Syndrome

Biallelic germline mutations in mismatch repair genes predispose to constitutional mismatch repair deficiency syndrome (CMMR-D). The condition is characterized by a broad spectrum of early-onset tumors, including hematological, brain and bowel and is frequently associated with features of Neurofibromatosis type 1. Few definitive screening recommendations have been suggested and no published reports have described predictive testing. We report on the first case of predictive testing for CMMR-D following the identification of two non-consanguineous parents, with the same heterozygous mutation in MLH1: c.1528C > T. The genetic counseling offered to the family, for their two at-risk daughters, is discussed with a focus on the ethical considerations of testing children for known cancer-causing variants. The challenges that are encountered when reporting on heterozygosity in a child younger than 18 years (disclosure of carrier status and risk for Lynch syndrome), when discovered during testing for homozygosity, are addressed. In addition, the identification of CMMR-D in a three year old, and the recommended clinical surveillance that was proposed for this individual is discussed. Despite predictive testing and presymptomatic screening, the sudden death of the child with CMMR-D syndrome occurred 6 months after her last surveillance MRI. This report further highlights the difficulty of developing guidelines, as a result of the rarity of cases and diversity of presentation.     

Exemplar similarity and rule application

We report four experiments examining effects of instance similarity on the application of simple explicit rules. We found effects of similarity to illustrative exemplars in error patterns and reaction times. These effects arose even though participants were given perfectly predictive rules, the similarity manipulation depended entirely on rule-irrelevant features, and attention to exemplar similarity was detrimental to task performance. Comparison of results across studies suggests that the effects are mandatory, non-strategic and not subject to conscious control, and as a result, should be pervasive throughout categorization.     

Olfactory-tactile compatibility effects demonstrated using a variation of the Implicit Association Test

We investigated whether the crossmodal associations between olfaction and touch reported previously in studies involving subjective report measures could also be demonstrated using an indirect measure of crossmodal association. To this end, we used a modified version of the Implicit Association Test. The participants had to make speeded discrimination responses to a series of unimodally presented olfactory (lemon vs. animal odour) or tactile stimuli (soft vs. rough fabric) using two response keys. In compatible blocks of trials, the olfactory and tactile stimuli that were mapped onto the same response key were considered to share a stronger association (e.g., the lemon odour and the soft fabric) than those that were combined onto the same response key in the incompatible blocks of trials (e.g., the animal odour and the soft fabric). The results showed that the participants responded significantly more rapidly in the compatible response mapping blocks than in the incompatible blocks, thus confirming the existence of associations between the stimuli that were considered to be compatible. These results provide the first empirical evidence that olfactory-tactile crossmodal associations are stable enough to influence performance even when not directly relevant to a participant’s task.     

Role Asymmetry and Code Transmission in Signaling Games: An Experimental and Computational Investigation

In signaling games, a sender has private access to a state of affairs and uses a signal to inform a receiver about that state. If no common association of signals and states is initially available, sender and receiver must coordinate to develop one. How do players divide coordination labor? We show experimentally that, if players switch roles at each communication round, coordination labor is shared. However, in games with fixed roles, coordination labor is divided: Receivers adjust their mappings more frequently, whereas senders maintain the initial code, which is transmitted to receivers and becomes the common code. In a series of computer simulations, player and role asymmetry as observed experimentally were accounted for by a model in which the receiver in the first signaling round has a higher chance of adjusting its code than its partner. From this basic division of labor among players, certain properties of role asymmetry, in particular correlations with game complexity, are seen to follow.     

Pecunia olet: the role of incidental disgust in the ultimatum game

We address the role of the incidental emotion of disgust in the Ultimatum Game. Participants had to choose whether or not to accept a ? offer from a ?0 pot made by another participant; 120 were in a room where a disgusting smell was released and 120 were in a room with no particular smell. Acceptance rates were higher in the room with the disgusting smell. The effect was mainly carried by the male participants who also reported more disgust with the disgusting smell and judged the offer as less unfair than females. We propose a spontaneous discounting explanation. Acceptance rates were higher in the room with the disgusting smell because participants misattributed the disgust induced by the offer to the ambient disgusting smell.     

Face detection in complex visual displays: an eye-tracking study with 3- and 6-month-old infants and adults

The ability to detect and prefer a face when embedded in complex visual displays was investigated in 3- and 6-month-old infants, as well as in adults, through a modified version of the visual search paradigm and the recording of eye movements. Participants (N=43) were shown 32 visual displays that comprised a target face among 3 or 5 heterogeneous objects as distractors. Results demonstrated that faces captured and maintained adults' and 6-month-olds' attention, but not 3-month-olds' attention. Overall, the current study contributes to knowledge of the capacity of social stimuli to attract and maintain visual attention over other complex objects in young infants as well as in adults.     

A Mobile Colonoscopic Unit for Lynch Syndrome: Trends in Surveillance Uptake and Patient Experiences of Screening in a Developing Country

The Genetic and Endoscopic Surveillance Clinic is an annual outreach service offering accessible colonoscopic surveillance to known families with Lynch syndrome living in remote areas of the Western and Northern Cape Province of South Africa. Unfortunately attendance at this outreach clinic has been declining over several years and fewer than a quarter of participants, attending for surveillance, have been adherent with all their recommended screening appointments. Concerns exist for non-adherent individuals as screening can prevent colorectal cancer by removing the precancerous lesion or enabling the treatment of a malignancy at an early stage. This study explored the experience of surveillance from both the non-adherers’ and adherers’ perspectives and identified unique factors affecting attendance at the outreach clinic. Rates of compliance are calculated for 191 mutation-positive cases of Lynch syndrome, using strict attendance criteria, and compared to figures obtained from self-reported attendance. Non-compliance was under-reported and compliance was exaggerated when basing data on self-reported adherence to recommendations. Specific characteristics of the outreach clinic affecting compliance are identified and recommendations are made to facilitate improvements to the service. These improvements can result in increased compliance with screening regimens and ultimately reduce cancer-related mortality.