Prevalence of gambling behaviours and their associations with socioemotional harm among 11-16 year olds in Wales: findings from the School Health Research Network survey

This is the final version. Available on open access from OUP via the DOI in this recordBACKGROUND: Gambling opportunities are increasingly available and acceptable to many adolescents. Adolescent problem gambling has been associated with poor outcomes, such as lower reported physical and mental health. While much research has focussed on 'problem' gambling, analysing the distribution and determinants of experimentation with gambling is important in order to understand its normalization and population level consequences. This study describes the distribution of inequalities and socioemotional harms associated with adolescent gambling. METHODS: Data were drawn from a subsample of students (N = 37 363) who completed gambling questions as part of the 2017 School Health Research Network Student Health and Wellbeing Survey, representing 193 secondary schools in Wales. Using imputations, we estimated a series of single-predictor and multi-predictor regressions for count of gambling behaviours, any gambling in the past 12 months and socioemotional harms of gambling. RESULTS: Approximately two-fifths (41.0%) of respondents reported gambling in the past 12 months, of whom 16.2% reported feeling bad as a result of their own gambling. We found significant sex differences in gambling, with boys gambling more frequently than girls. Adolescents from more affluent families reported a higher count of gambling behaviours and socioemotional harms, although paradoxically, increasing affluence was also associated with lower prevalence of gambling in the last year. Non-White British ethnicities and students who felt less connected to school were more likely to engage in gambling and experience socioemotional harms. CONCLUSIONS: Our findings provide important new insights regarding risk factors in adolescence associated with gambling behaviours and socioemotional harms.British Heart FoundationCancer Research UKEconomic and Social Research Council (ESRC)Medical Research Council (MRC)Welsh GovernmentWellcome Trus

The diffusion of IP telephony and vendors' commercialisation strategies

This is a post-peer-review, pre-copyedit version of an article published in the Journal of Information Technology. The definitive publisher-authenticated version is available at the link below.The Internet telephony (IP telephony) has been presented as a technology that can replace existing fixed-line services and disrupt the telecommunications industry by offering new low-priced services. This study investigates the diffusion of IP telephony in Denmark by focusing on vendors’ commercialisation strategies. The theory of disruptive innovation is introduced to investigate vendors’ perceptions about IP telephony and explore their strategies that affect the diffusion process in the residential market. The analysis is based on interview data collected from the key market players. The study's findings suggest that IP telephony is treated as a sustaining innovation that goes beyond the typical voice transmission and enables provision of advanced services such as video telephony

Titanium Nitride Films for Ultrasensitive Microresonator Detectors

Titanium nitride (TiNx) films are ideal for use in superconducting microresonator detectors because: a) the critical temperature varies with composition (0 < Tc < 5 K); b) the normal-state resistivity is large, \rho_n ~ 100 $\mu$Ohm cm, facilitating efficient photon absorption and providing a large kinetic inductance and detector responsivity; and c) TiN films are very hard and mechanically robust. Resonators using reactively sputtered TiN films show remarkably low loss (Q_i > 10^7) and have noise properties similar to resonators made using other materials, while the quasiparticle lifetimes are reasonably long, 10-200 $\mu$s. TiN microresonators should therefore reach sensitivities well below 10^-19 WHz^(-1/2).Comment: to be published in AP

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

Purpose To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. Methods Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), “cone dystrophy with supernormal rod ERG” (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM). Results In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change. Conclusions Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention

rRNA sequencing in molecular microbiological diagnosis of bacterial infections in the autopsy setting

Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material

A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

PurposeTo describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.MethodsUsing direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.ResultsOnly one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.ConclusionsMutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2

Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy

In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with “cone-first” retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs∗2];[Glu529Valfs∗2], and c.[401delT(;)3354G>A], p.[Leu134Argfs∗45(;)Trp1118∗]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543∗) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families

High-resolution optical coherence tomography imaging in KCNV2 retinopathy

ABSTRACT Aim To report novel spectral domain optical coherence tomography (SD-OCT) findings and new mutational data in patients with &apos;cone dystrophy with supernormal rod electroretinogram&apos;, a recessive childhood onset retinal dystrophy consequent upon mutation in the KCNV2 gene. Design/methods This was a comparative case series study of 12 patients with clinical and/or electrophysiological findings in keeping with KCNV2 mutation. Clinical examination and electrophysiological testing results were reviewed. Fundus photography and autofluorescence imaging were performed. Retinal layer appearance and thickness were evaluated using SD-OCT. The coding region and introneexon boundaries of KCNV2 were screened by direct sequencing. Results Mutations in KCNV2 were detected in all families; five of these changes were novel. Pattern electroretinograms were undetectable and full-field electroretinograms showed findings specific for the disorder