rBahadur: efficient simulation of structured high-dimensional genotype data with applications to assortative mating.

Existing methods for generating synthetic genotype data are ill-suited for replicating the effects of assortative mating (AM). We propose rb_dplr, a novel and computationally efficient algorithm for generating high-dimensional binary random variates that effectively recapitulates AM-induced genetic architectures using the Bahadur order-2 approximation of the multivariate Bernoulli distribution. The rBahadur R library is available through the Comprehensive R Archive Network at https://CRAN.R-project.org/package=rBahadur .

European Society for the Study of Tourette Syndrome 2022 criteria for clinical diagnosis of functional tic-like behaviours: International consensus from experts in tic disorders.

BACKGROUND AND PURPOSE: In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic-like behaviours. We assembled a working group to develop criteria for the clinical diagnosis of functional tic-like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition. METHODS: We used a formal consensus development process, using a multiround, web-based Delphi survey. The survey was based on an in-person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting. RESULTS: In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion. CONCLUSIONS: Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity.

The spectrum of functional tic-like behaviours: Data from an international registry.

BACKGROUND AND PURPOSE: Between 2019 and 2022, there was a marked rise in adolescents/young adults seeking urgent help for functional tic-like behaviours (FTLBs). Given the global scale of this phenomenon, we aimed to pool cases from different institutions in an international registry to better characterize this spectrum and facilitate future longitudinal observation. METHODS: An international collaborative group from 10 tertiary referral centres for tic disorders collected retrospective data on FTLB patients who sought specialists' attention between the last quarter of 2019 and June 2022. An audit procedure was used for collection of data, which comprised demographics, course of presentation and duration, precipitating and predisposing factors, phenomenology, comorbidities, and pharmacological treatment outcome. RESULTS: During the study period, we collected data on 294 patients with FTLBs, 97% of whom were adolescents and young adults and 87% of whom were female. FTLBs were found to have a peak of severity within 1 month in 70% of patients, with spontaneous remissions in 20%, and a very high frequency of complex movements (85%) and vocalizations (81%). Less than one-fifth of patients had pre-existing primary tic disorder, 66% had comorbid anxiety disorders, 28% comorbid depressive disorders, 24% autism spectrum disorder and 23% attention deficit/hyperactivity disorder. Almost 60% explicitly reported exposure to tic-related social media content. The vast majority of pharmacologically treated patients did not report benefit with tic-suppressing medications. CONCLUSIONS: Our data from the largest multicentre registry of FTLBs to date confirm substantial clinical differences from primary tic disorders. Social modelling was the most relevant contributing factor during the pandemic. Future longitudinal analyses from this database may help understand treatment approaches and responsiveness.

Commentary: What is unsought will go undetected - a commentary on Rodin et al. (2020).

Rodin et al.'s study (2020) on the belief, knowledge and attitudes about tics amongst health professionals in Uganda is a preliminary yet an important step towards challenging the current thinking amongst clinicians and academics working with tics, which is that tics are hardly seen in or are absent in the sub-Saharan African population and it has been psotulated that this phenomenon is considered to be explained by genetics.

Commentary: PDA - what's in a name? Dimensions of difficulty in children reported to have an ASD and features of extreme/pathological demand avoidance: a commentary on O'Nions et al. (2017).

Pathological demand avoidance (PDA), a term first used by Elizabeth Newson in the 1980s, refers to a collection of behaviours that children will demonstrate to avoid instructions (and tasks) that they perceive as demands. These children are postulated to be averse to anything that is perceived as a demand placed on them. PDA features are commonly encountered in children with autism but PDA is not a subtype of autism nor a separately diagnosed mental, behavioural or developmental disorder in any of the major classification systems (ICD-10 or DSM-5). Such behaviours are not confined to children with autism and debate continues regarding its existence as a distinct phenomenon and if such a phenotype exists whether it is merely a part of autism or a separate condition. We comment on O'Nions and colleagues' study that explores common themes/behavioural traits in children with autism spectrum disorder (ASD) who also fit the phenotypic description of PDA. We explore how the current classification systems capture features of PDA in autism with diagnoses of common comorbidities in ASD (such as disruptive behaviour/conduct disorders, OCD and anxiety), but to many clinicians and parents this seems an inadequate description. What remains to be explored are the trans-diagnostic temperamental and cognitive traits of children with PDA features, such as cognitive rigidity and intolerance of uncertainty. It is important to understand why some children are demand avoidant and identification of these factors (individual and systemic) helps in management much more than classifying them with an additional label. O'Nions et al. have helpfully provided further insight into several underpinning traits/dimensions of children with PDA features; understanding these will help develop effective strategies for parenting demand-avoidant children.

Intense Imagery Movements May Lead to Maladaptive Daydreaming: A Case Series and Literature Review.

BACKGROUND: This case series highlights the connection between childhood intense imagery movements (IIM) and adult-reported maladaptive daydreaming (MD). Motor stereotypies occur in typically developing children and also with co-occurring neurodevelopmental differences. A subgroup with complex motor stereotypies reports accompanying intense imagery, often enhanced by the movements. This phenomenon can persist into adulthood and, in some cases, will need active management to prevent significant distress and impairment. CASES: Six adults, self-reporting maladaptive daydreaming associated with stereotypies, are presented to demonstrate the associations. LITERATURE REVIEW: The clinical significance and function of IIM and MD are unclear, but several hypotheses are discussed, including the mechanism of emotional regulation through sensory seeking, as a process for processing childhood psychological trauma, as intrusive thoughts or images as part of a subtype of Obsessive Compulsive Disorder, or as a result of diverse attentional networks seen in neurodevelopmental disorders. CONCLUSIONS: This paper highlights important connections between IIM and MD. Many adults with MD show a childhood origin of stereotypical movements. Whilst immersive daydreaming may provide creativity and emotional regulation, there is evidence of distress and impairment of function for some adults, leading to MD diagnoses. Recognizing this phenomenon is important for all neurologists and physicians working with stereotypical movements.

The changing landscape of childhood tic disorders following COVID-19.

The article describes classification, aetiology and features of typical tic disorders (Tourette syndrome) and their management with an additional focus on a surge in atypical tic presentations following the COVID-19 pandemic, often described as functional tics, or functional tic-like movements. We discuss what explains their atypical nature and what might underpin this increase in incidence. Lastly the article provides an overview of management of functional tics, so readers can understand how management of these differs from typical tic disorders.

Paediatric tic-like presentations during the COVID-19 pandemic.

BACKGROUND AND AIM: Clinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described. METHODS: A retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months. RESULTS: 94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety. CONCLUSION: We highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies.

Crescentic Glomerulonephritis and Membranous Nephropathy: A Rare Overlap.

Background: Membranous nephropathy (MN) is a disease that affects the basement membrane of the glomeruli of the kidney resulting in proteinuria. The concurrent incidence of vasculitic glomerulonephritis and MN in the same patient is unusual. Herein, we report a case with this unusual combination. Case: Our patient is a 53-year-old Hispanic male with a medical history of tobacco use, type 2 diabetes mellitus, and hypertension who presented with hematuria and was found to have nephrotic range proteinuria and renal impairment. Blood workup revealed positive ANCA serology, which led to a renal biopsy that showed crescentic vasculitis in addition to membranous nephropathy. The patient was started on intermittent hemodialysis (HD) and treated initially with intravenous (IV) pulse steroids; subsequently, oral prednisolone and IV cyclophosphamide were initiated. The patient remained HD dependent at the time of discharge with the resolution of hematuria. A follow-up with an outpatient nephrology clinic was arranged. Conclusion: Membranous nephropathy complicated by crescentic glomerulonephritis has a more aggressive clinical course and decline in renal function compared to MN alone which can lead to initiating renal replacement therapy. However, immunosuppressive drugs can result in significant improvement of renal function if started early enough.

Clinical management of complex motor stereotypies.

This paper will review complex motor stereotypies and provide a summary of the current proposed treatment pathway.

Binary matrix factorization on special purpose hardware.

Many fundamental problems in data mining can be reduced to one or more NP-hard combinatorial optimization problems. Recent advances in novel technologies such as quantum and quantum-inspired hardware promise a substantial speedup for solving these problems compared to when using general purpose computers but often require the problem to be modeled in a special form, such as an Ising or quadratic unconstrained binary optimization (QUBO) model, in order to take advantage of these devices. In this work, we focus on the important binary matrix factorization (BMF) problem which has many applications in data mining. We propose two QUBO formulations for BMF. We show how clustering constraints can easily be incorporated into these formulations. The special purpose hardware we consider is limited in the number of variables it can handle which presents a challenge when factorizing large matrices. We propose a sampling based approach to overcome this challenge, allowing us to factorize large rectangular matrices. In addition to these methods, we also propose a simple baseline algorithm which outperforms our more sophisticated methods in a few situations. We run experiments on the Fujitsu Digital Annealer, a quantum-inspired complementary metal-oxide-semiconductor (CMOS) annealer, on both synthetic and real data, including gene expression data. These experiments show that our approach is able to produce more accurate BMFs than competing methods.

Functional neurological movements in children: Management with a psychological approach.

AIM: To develop a cognitive behavioural treatment (CBT) approach that included novel attention training components to support symptom management in children with a primary diagnosis of Functional Movement Disorder (FMD). METHOD: Eighteen children (9 male and 9 female) with a mean age of 13 years (sd = 2.46, range 10-18 years) were assessed and completed CBT with novel attention training components. Treatment outcomes were measured using the Child Global Assessment Scale (CGAS) which was administered at baseline and post-treatment. RESULTS: Scores on the CGAS improved significantly post-treatment (p < 0.001) with all participants showing significant change in functioning on the basis of the Reliable Change Index (RCI), with clinically significant change across classification boundaries. INTERPRETATION: This case series provides support for the use of CBT with attention training components for the management of FMD. Larger trials are necessary to identify which individual treatment components are most effective and to better understand and quantify response to treatment. Future clinical treatment studies would benefit from the inclusion of objective measures of interoception and attentional focus.

Misophonia in Children with Tic Disorders: A Case Series.

OBJECTIVE: Misophonia is a condition characterized by the dislike or hatred (miso) of specific sounds (phonia) that results in an extreme emotional response. There has been growing interest in misophonia, with emerging evidence from neurodevelopmental populations and ongoing debate regarding the psychiatric classification and the mechanisms underlying this phenomenon. This is the first article to report on misophonic experiences and associated clinical characteristics in young people with tic disorders. METHOD: In this article, we present the cases of 12 children and young people with tic disorders who have attended clinics in the United Kingdom and Italy who report misophonia. Misophonia was classified as a selective aversive response in accordance with the criteria proposed by Schröder. RESULTS: These cases support the view that a range of auditory stimuli may lead to negative/aversive emotional responses of varying degrees, with misophonia seeming to contribute to behavioral reactions. Among these, the most frequent was anger outbursts, followed by an increase in tics, trigger avoidance, repetition of the sound, and self-injurious behavior. No single treatment approach was effective, with some patients responding to cognitive behavioral therapies and others to pharmacological support. CONCLUSION: We postulate that misophonia could be an underestimated causative phenomenon for abrupt emotional dysregulation in individuals with tic disorders and should be considered as part of a comprehensive clinical assessment. This article presents findings of relevance to general discussions regarding the classification of misophonia, as well as the potential relationship between sensory abnormalities and the broader phenotype of tic disorders during development.

Pathological Demand Avoidance: symptoms but not a syndrome.

Pathological (or extreme) demand avoidance is a term sometimes applied to complex behaviours in children within-or beyond-autism spectrum disorder. The use of pathological demand avoidance as a diagnosis has, at times, led to altered referral practice and misunderstandings between professionals and the families of patients. In our Viewpoint, we reviewed the current literature and conclude that the evidence does not support the validity of pathological demand avoidance as an independent syndrome. Nevertheless, the use of the term highlights an important known range of co-occurring difficulties for many children with autism spectrum disorder that can substantially affect families. We explore how these difficulties can best be understood through understanding of social, sensory, and cognitive sensitivities in autism spectrum disorder, identification of frequently occurring comorbid conditions, and assessment of how these problems interact within the child's social environment. Such understanding should then inform individualised management strategies for children and families, and in social settings, such as education. It is crucial that a shared understanding is achieved between professionals and families in this area.

Children after adoption: Exploring their psychological needs.

Children adopted from care are known to be at increased risk for mental health difficulties although relatively little research has been carried out to explore this question. This study assessed the mental health and psychological development of children placed for adoption by one UK Local Authority. We compared the pattern and prevalence of difficulties to existing data including that on Looked-After Children (LAC) children. Totally, 106 families were initially approached and parent interviews and at least partial questionnaire data were gathered on 47 children, 72.3% of whom were known to have been maltreated prior to adoption. Of the 34 children with a complete data set including Development and Well-Being Assessment (DAWBA), 76.4% met full criteria for at least one neurodevelopmental or mental health diagnosis, a markedly higher rate than comparison data on LAC or community samples. Less than half of those identified with a mental health diagnosis had received any prior diagnosis, and only a minority had received appropriate services. Despite the children's difficulties, the great majority of parents reported high enjoyment of bringing up their child.