Stochastic oscillations of adaptive networks: application to epidemic modelling

Adaptive-network models are typically studied using deterministic differential equations which approximately describe their dynamics. In simulations, however, the discrete nature of the network gives rise to intrinsic noise which can radically alter the system's behaviour. In this article we develop a method to predict the effects of stochasticity in adaptive networks by making use of a pair-based proxy model. The technique is developed in the context of an epidemiological model of a disease spreading over an adaptive network of infectious contact. Our analysis reveals that in this model the structure of the network exhibits stochastic oscillations in response to fluctuations in the disease dynamic.Comment: 11 pages, 4 figure

Genomics and insurance in the United Kingdom: Increasing complexity and emerging challenges

This article identifies issues relating to the use of genetics and genomics in insurance that may challenge existing regulatory models in the UK and elsewhere. We discuss three core issues: (1) As genomic testing advances, and results are increasingly relevant to guide healthcare across an individual's lifetime, the distinction between diagnostic and predictive testing that the current UK insurance code relies on becomes more blurred and this has consequences what constitutes a genetic “result” (2) The emerging category of pharmacogenomic tests which are predictive only the in the context of a specific prescribing moment (3) The increasing availability and affordability of polygenic scores that are neither clearly diagnostic nor highly predictive, but which nonetheless might have incremental value for insurance underwriting beyond conventional factors. We also outline the broad scope of possible regulatory responses to these developments. At present in the UK, consumers are not obliged to declare results of predictive genetic tests except in very specific scenarios, meaning that pricing is not actuarially fair (premiums paid in such cases are likely to be lower than the expected value of the compensation received). We suggest a deliberative approach is required to establish where these deviations from actuarially fair pricing should be upheld, and whether there might be situations in which they should be withdrawn

Impact of practice on quality of life of those living with an indwelling urinary catheter - an international evaluation

After completing this education activity, the learner will be able to compare the characteristics and quality of life of patients living with a long-term indwelling urinary catheter in the United Kingdom and the United States where catheter care policies differ with respect to types and routes of catheterization and timing of catheter changes

Recoiling from a kick in the head-on collision of spinning black holes

Recoil ``kicks'' induced by gravitational radiation are expected in the inspiral and merger of black holes. Recently the numerical relativity community has begun to measure the significant kicks found when both unequal masses and spins are considered. Because understanding the cause and magnitude of each component of this kick may be complicated in inspiral simulations, we consider these effects in the context of a simple test problem. We study recoils from collisions of binaries with initially head-on trajectories, starting with the simplest case of equal masses with no spin and then adding spin and varying the mass ratio, both separately and jointly. We find spin-induced recoils to be significant relative to unequal-mass recoils even in head-on configurations. Additionally, it appears that the scaling of transverse kicks with spins is consistent with post-Newtonian theory, even though the kick is generated in the nonlinear merger interaction, where post-Newtonian theory should not apply. This suggests that a simple heuristic description might be effective in the estimation of spin-kicks.Comment: 12 pages, 10 figures. Replaced with published version, including more discussion of convergence and properties of final hol

Dynamics Among Borderline Personality and Anxiety Features in Psychotherapy Outpatients: An Exploration of Nomothetic and Idiographic Patterns

Borderline personality disorder (BPD) involves instability in self-concept, emotions, and behavior. However, the dynamic, longitudinal relations among BPD symptoms and between these symptoms and other problematic emotional experiences are poorly understood. It is also unclear whether these dynamics are the same across persons (including across diagnostic boundaries), specific to individuals with BPD, or idiographic. The current study uses ecological momentary assessment and Group Iterative Multiple Model Estimation (GIMME), a novel, data-driven approach to identifying dynamic patterns in time-series data at group, subgroup, and individual levels, to investigate the dynamic connections among select features of BPD (anger, impulsivity, and identity disturbance) and anxiety-related experiences. Forty-two psychiatric outpatients diagnosed with BPD (n = 27) or with an anxiety disorder, but not BPD (n = 15) rated their anger, identity disturbance, impulsivity, anxiety, stress, and calmness states six times per day for 21 days, providing a total of 4,699 surveys. Only one dynamic link between symptoms was identified that applied at the group level, and GIMME did not reveal stable subgroups of individuals with distinct symptom dynamics. Instead, these dynamics differed from individual to individual. These results suggest that connections among these BPD and anxiety symptoms do not depend on diagnosis and are somewhat idiographic. Case examples are used to illustrate the clinical utility of within-person symptom models as a supplement to traditional diagnostic information

Heparanase 2, mutated in urofacial syndrome, mediates peripheral neural development in Xenopus

Urofacial syndrome (UFS; previously Ochoa syndrome) is an autosomal recessive disease characterized by incomplete bladder emptying during micturition. This is associated with a dyssynergia in which the urethral walls contract at the same time as the detrusor smooth muscle in the body of the bladder. UFS is also characterized by an abnormal facial expression upon smiling, and bilateral weakness in the distribution of the facial nerve has been reported. Biallelic mutations in HPSE2 occur in UFS. This gene encodes heparanase 2, a protein which inhibits the activity of heparanase. Here, we demonstrate, for the first time, an in vivo developmental role for heparanase 2. We identified the Xenopus orthologue of heparanase 2 and showed that the protein is localized to the embryonic ventrolateral neural tube where motor neurons arise. Morpholino-induced loss of heparanase 2 caused embryonic skeletal muscle paralysis, and morphant motor neurons had aberrant morphology including less linear paths and less compactly-bundled axons than normal. Biochemical analyses demonstrated that loss of heparanase 2 led to upregulation of fibroblast growth factor 2/phosphorylated extracellular signal-related kinase signalling and to alterations in levels of transcripts encoding neural- and muscle-associated molecules. Thus, a key role of heparanase 2 is to buffer growth factor signalling in motor neuron development. These results shed light on the pathogenic mechanisms underpinning the clinical features of UFS and support the contention that congenital peripheral neuropathy is a key feature of this disorder

A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families

HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females

The Implementation of Pharmacogenetics in the United Kingdom.

There is considerable inter-individual variability in the effectiveness and safety of pharmaceutical interventions. This phenomenon can be attributed to a multitude of factors; however, it is widely acknowledged that common genetic variation affecting drug absorption or metabolism play a substantial contributory role. This is a concept known as pharmacogenetics. Understanding how common genetic variants influence responses to medications, and using this knowledge to inform prescribing practice, could yield significant advantages for both patients and healthcare systems. Some health services around the world have introduced pharmacogenetics into routine practice, whereas others are less advanced along the implementation pathway. This chapter introduces the field of pharmacogenetics, the existing body of evidence, and discusses barriers to implementation. The chapter will specifically focus on efforts to introduce pharmacogenetics in the NHS, highlighting key challenges related to scale, informatics, and education