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.     

Imagining the future in health anxiety: the impact of rumination on the specificity of illness-related memory and future thinking

Individuals with health anxiety experience catastrophic fears relating to future illness. However, little research has explored cognitive processes involved in how health anxious individuals picture the future. Ruminative thinking has been shown to impede the ability to recall specific autobiographical memories, which in turn is related to maladaptive, categoric future thinking processes. This study examined the impact of rumination on memory and future thinking among 60 undergraduate participants with varying health anxiety (35% clinical-level health anxiety). Participants were randomized to experiential/ruminative self-focus conditions, then completed an Autobiographical Memory Test and Future Imaginings Task. Responses were coded for specificity and the presence of illness concerns. Rumination led to more specific illness-concerned memories overall, yet at the same time led to more categoric illness-related future imaginings. Rumination and health anxiety together best predicted overgeneral illness-related future imaginings. Highly specific illness-related memories may be maintained due to their personal salience. However, more overgeneral illness-related future imaginings may reflect cognitive avoidance in response to the threat of future illness. This divergent pattern of results between memory and future imaginings may exacerbate health anxiety, and may also serve to maintain maladaptive responses among individuals with realistic medical concerns, such as individuals living with chronic illness.     

Beauty or function? How different mass customization toolkits affect customers' process enjoyment

Although it is widely acknowledged that mass customization (MC) increases both company and customer value, the research has neglected the possible effects of different MC toolkits on customer responses. In this study, we investigate the influence of different MC toolkits on customers' process enjoyment by manipulating the extent to which those toolkits allow customers to customize a product's functional attributes (functional MC toolkits), aesthetic attributes (aesthetic MC toolkits), or both (supreme toolkits). In addition, we examine the moderating effect of customers' ability to customize. The results of two experimental studies show that regardless of their ability to customize, customers' process enjoyment is higher with an aesthetic MC toolkit than with a functional MC toolkit. For customers with a high ability to customize, process enjoyment with a supreme toolkit is higher than process enjoyment with an aesthetic toolkit, whereas no differences exist for customers with a low ability to customize. This research contributes significantly to the existing literature on mass customization and provides managers with insights on how to more effectively develop and implement MC toolkits. Copyright © 2015 John Wiley & Sons, Ltd.     

The Combined Effect of Neuropsychological and Neuropathological Deficits on Instrumental Activities of Daily Living in Older Adults: a Systematic Review

To date, studies have consistently demonstrated associations between either neuropsychological deficits or neuroanatomical changes and instrumental activities of daily living (IADL) in aging. Only a limited number of studies have evaluated morphological brain changes and neuropsychological test performance concurrently in relation to IADL in this population. As a result, it remains largely unknown whether these factors independently predict functional outcome. The current systematic review intended to address this lack of information by reviewing the literature on older adults, incorporating studies that examined e.g., normal aging, but also stroke or dementia patients. A comprehensive search of databases (Pubmed, Embase, Medline, Web of Science, PsycINFO) and reference lists was performed, focusing on papers in the English language that examined the combined effect of neuropsychological and neuroanatomical factors on IADL in samples of adults with an average age above 50. In total, 58 potential articles were identified; 20 were included in the review. The results show that especially neuropsychological variables (primarily memory and executive functions) independently predict IADL. Although some unique predictive value of brain morphological changes, such as hippocampal atrophy, was found, support for the importance of white matter changes was limited. However, the results of the studies reviewed are diverse, and appear to be at least partially determined by the variables included. For example, studies were less likely to find an independent effect of cognition if they solely employed a cognitive screening instrument. This indicates that a structured examination of neuroanatomical and neuropsychological correlates of IADL in different patient populations is warranted.     

How to rapidly construct a spatial–numerical representation in preliterate children (at least temporarily)

Spatial processing of numbers has emerged as one of the basic properties of humans’ mathematical thinking. However, how and when number–space relations develop is a highly contested issue. One dominant view has been that a link between numbers and left/right spatial directions is constructed based on directional experience associated with reading and writing. However, some early forms of a number–space link have been observed in preschool children who cannot yet read and write. As literacy experience is evidently not necessary for number–space effects, we are searching for other potential sources of this association. Here we propose and test a hypothesis that the number–space link can be quickly constructed in preschool children's cognition on the basis of spatially oriented visuo‐motor activities. We trained 3‐ and 4‐year‐old children with a non‐numerical spatial movement task (left‐to‐right or right‐to‐left), where via touch screen children had to move a frog across a pond. After the training, children had to perform a numerosity comparison task. After left‐to‐right training, we observed a SNARC‐like effect (reactions to smaller numbers were faster on the left side, and reactions to larger numbers on the right side), and after right‐to‐left training a reverse effect. These results are the first to show a causal link between visuo‐motor activities and number–space associations in children before they learn to read and write. We argue that simple activities, such as manual games, dominant in a given society, might shape number–space associations in children in a way similar to lifelong reading training.     

Social cognition and social functioning in patients with amnestic mild cognitive impairment or Alzheimer’s dementia

The aim of the present study was to examine social cognition and social functioning in a group of amnestic mild cognitive impairment (aMCI) and Alzheimer’s dementia (AD) patients. Thirty one people with aMCI, 29 individuals with AD, and 45 healthy older adults participated in the study. Facial expressions of happiness, anger, fear, disgust, and surprise presented in different intensities had to be labelled. Mentalizing was assessed using first-order belief theory of mind (ToM) stories and everyday social functioning by the Inventory of Interpersonal Situations (IIS), completed by an informant. aMCI patients were impaired in recognizing the emotions anger, disgust, and fear, while AD patients were impaired in recognizing the emotions anger, disgust, and surprise. More importantly, no significant differences between aMCI and AD patients were found on overall emotion recognition. Both the aMCI and AD patients were impaired on the ToM task, but no differences between the aMCI and AD patients were found. On everyday social functioning, only the AD patients showed impairments. No associations between the IIS and ToM were found, but the IIS and emotion perception were significantly correlated. Regression analysis taking all potentially confounding variables into account showed that only mood, but not the social-cognitive task performance or any other cognitive variable, predicted social functioning. aMCI and AD patients demonstrated impairments in mentalizing and facial emotion perception, and showed decrements in everyday social functioning. Informing caregivers about these deficits may help them to understand deficits in social cognition that may be present already in the MCI stage of Alzheimer’s disease.     

Being moved by meaningfulness: appraisals of surpassing internal standards elicit being moved by relationships and achievements

ABSTRACT

People can be moved and overwhelmed, a phenomenon typically accompanied by goose-bumps and tears. We argue that these feelings of being moved are not limited to situations that are appraised as pro-social but elicited when someone surpasses an internal standard. In line with these predictions, people were moved by relationships and success (Study 1), by reunion, separation, success and failure (Study 2) and by social, environmental and sports achievements (Study 3). In all three studies, the elicitation of these feelings was partially mediated by appraisals of surpassing social or achievement standards. In line with this, ratings of meaningfulness were closely associated with feelings of being moved and moving stimuli elicited behavioural intentions such as spending time with family and friends, helping others and/or achieving something in life. Thus, moving situations may remind us about what we perceive as meaningful and thereby help us to act accordingly.     

What emotional reactions can tell us about the nature of others: An appraisal perspective on person perception

The present research aimed to assess how people use knowledge about the emotional reactions of others to make inferences about their character. Specifically, we postulate that people can reconstruct or “reverse engineer” the appraisals underlying an emotional reaction and use this appraisal information to draw person perception inferences. As predicted, a person who reacted with anger to blame was perceived as more aggressive, and self-confident, but also as less warm and gentle than a person who reacted with sadness (Study 1). A person who reacted with a smile (Study 1) or remained neutral (Study 2) was perceived as self-confident but also as unemotional. These perceptions were mediated by perceived appraisals.     

The role of causal attribution in hurt feelings and related social emotions elicited in reaction to other's feedback about failure

The present research addressed the question of what it is that makes certain types of feedback on the reasons for failure hurtful. The results of two studies demonstrated that the causal structure implied by an explanation for failure explains the degree to which the explanation is perceived as hurtful and likely to elicit anger, shame, and guilt. In contrast, the perceived validity of the explanations is of relatively less importance for the elicitation of hurt feelings and anger than the content of the explanation. Overall, these results provide further evidence for the importance of attributional information for social emotions, whereas the validity of the information had a relatively lesser effect.