Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader-Willi syndrome chromosome 15 q11-q13 deletion and boys with Fragile X syndrome

Prader-Willi syndrome (PWS) and Fragile X syndrome (FraX) are associated with distinctive cognitive and behavioural profiles. We examined whether repetitive behaviours in the two syndromes were associated with deficits in specific executive functions. PWS, FraX, and typically developing (TD) children were assessed for executive functioning using the Test of Everyday Attention for Children and an adapted Simon spatial interference task. Relative to the TD children, children with PWS and FraX showed greater costs of attention switching on the Simon task, but after controlling for intellectual ability, these switching deficits were only significant in the PWS group. Children with PWS and FraX also showed significantly increased preference for routine and differing profiles of other specific types of repetitive behaviours. A measure of switch cost from the Simon task was positively correlated to scores on preference for routine questionnaire items and was strongly associated with scores on other items relating to a preference for predictability. It is proposed that a deficit in attention switching is a component of the endophenotypes of both PWS and FraX and is associated with specific behaviours. This proposal is discussed in the context of neurocognitive pathways between genes and behaviour.

A question of taste: Recognising the role of latent preferences and attitudes in analysing food choices

There has long been substantial interest in understanding consumer food choices, where a key complexity in this context is the potentially large amount of heterogeneity in tastes across individual consumers, as well as the role of underlying attitudes towards food and cooking. The present paper underlines that both tastes and attitudes are unobserved, and makes the case for a latent variable treatment of these components. Using empirical data collected in Northern Ireland as part of a wider study to elicit intra-household trade-offs between home-cooked meal options, we show how these latent sensitivities and attitudes drive both the choice behaviour as well as the answers to supplementary questions. We find significant heterogeneity across respondents in these underlying factors and show how incorporating them in our models leads to important insights into preferences. 

It's not that I don't care, I just don't care very much: confounding between attribute non-attendance and taste heterogeneity

With the growing interest in the topic of attribute non-attendance, there is now widespread use of latent class (LC) structures aimed at capturing such behaviour, across a number of different fields. Specifically, these studies rely on a confirmatory LC model, using two separate values for each coefficient, one of which is fixed to zero while the other is estimated, and then use the obtained class probabilities as an indication of the degree of attribute non-attendance. In the present paper, we argue that this approach is in fact misguided, and that the results are likely to be affected by confounding with regular taste heterogeneity. We contrast the confirmatory model with an exploratory LC structure in which the values in both classes are estimated. We also put forward a combined latent class mixed logit model (LC-MMNL) which allows jointly for attribute non-attendance and for continuous taste heterogeneity. Across three separate case studies, the exploratory LC model clearly rejects the confirmatory LC approach and suggests that rates of non-attendance may be much lower than what is suggested by the standard model, or even zero. The combined LC-MMNL model similarly produces significant improvements in model fit, along with substantial reductions in the implied rate of attribute non-attendance, in some cases even eliminating the phenomena across the sample population. Our results thus call for a reappraisal of the large body of recent work that has implied high rates of attribute non-attendance for some attributes. Finally, we also highlight a number of general issues with attribute non-attendance, in particular relating to the computation of willingness to pay measures.

Evidence-based management and intervention for autism spectrum disorders

Autism Spectrum Disorder (ASD) is diagnosed along a continuum of behavioural variants in social communication and repetitive behaviours [96]. Most individuals on the autism spectrum also experience differences in sensory perception. Some individuals on the spectrum are ‘high-functioning’ and able to cope in every day environments, while others are severely affected, non-verbal, and may have co-occurring diagnoses, such as intellectual disability, epilepsy, and/or obsessional, conduct, or mental health disorders. These individuals require substantial support, caring and careful management, and evidence-based, effective interventions.

The Pinnacle of Popular Taste?: The Importance of Confessions of a Window Cleaner (1974)

Loathed by critics, the British sexploitation comedy Confessions of a Window Cleaner (1974) was dismissed as tawdry and vulgar yet its massive popular appeal makes it an important indicator of popular taste in the much-maligned 1970s. Using new archival material, this article examines what the film offered and how it was deliberately crafted in order to appeal to a variety of audiences.

A Zoologist with a Taste for the Past: The Earl of Cranbrook’s Contribution to Zooarchaeological Research in Southeast Asia

The Earl of Cranbrook (V) (then Lord Medway) was fi rst introduced to archaeological research in 1958 when he participated in excavations at the Niah Caves, Sarawak Borneo. In that same year he published a paper entitled ‘Food bone in Niah Cave excavations (-1958)’ in the Sarawak Museum Journal. Unbeknownst to him at the time, his individual and intuitive research was on a par with, if not methodologically ahead of, burgeoning studies in the fi eld of zooarchaeology that were taking place at leading academic institutions in Europe and the United States. This paper recounts and lauds the signifi cant contributions the Earl of Cranbrook has made to the establishment and furtherance of a discipline over more than 50 years. 

Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis, perturbation of which leads to masculinization disorders in rodents

Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal 'masculinization programming window'. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ~3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.