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In this chapter, we discuss a speculative and participatory “media architecture” installation that engages people with the potential impacts of data through speculative future images of the datafied city. The installation was originally conceived as a physical combination of digital media technologies and architectural form—a “media architecture”—that was to be situated in a particular urban setting. Due to the COVID-19 pandemic, however, it was produced and tested for an online workshop. It is centered on “design frictions” (Forlano and Mathew, 2014) and processes of controversing (Baibarac-Duignan and de Lange, 2021). Instead of smoothing out tensions through “neutral” data visualizations, controversing centers on opening avenues for meaningful participation around frictions and controversies that arise from the datafication of urban life. The installation represents an instance of how processes of controversing may unfold through digital interfaces. Here, we explore its performative potential to “interface” abstract dimensions of datafication, “translate” them into collective issues of concern, and spark imagination around (un)desirable datafied urban futures.

Item does not contain fulltext, Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Introduction: Epinephrine continues to be a fundamental part of the Advanced Cardiac Life Support algorithm despite a lack of evidence that it improves neurologically intact survival. Our aim was both to identify a potential upper limit of epinephrine use in resuscitations and to demonstrate real-world epinephrine use in different patient subgroups.Methods: This was a single-center, retrospective cohort study, conducted between August 1, 2016–July 1, 2021, of patients with medical cardiac arrest who were administered a known number of epinephrine doses. The primary outcome was neurologically intact discharge defined by a modified Rankin scale ≤3, with secondary outcomes of comparing epinephrine doses by age, rhythm, and emergency medical services vs emergency department administration of epinephrine.Results: The study included 1,330 patients, with 184 patients (13.8%) surviving to neurologically intact discharge. The primary outcome of neurologically intact discharge was found in 89 (65.4%) patients in the zero epinephrine dose group, 75 (20.0%) in the 1-3 dose group, 15 (4.3%) in the 4-6 dose group, and one (0.002%) in the ≥7 dose group (P < 0.001). Patients received similar amounts of epinephrine when stratified by age, while patients with shockable rhythms received more epinephrine than patients with non-shockable rhythms.Conclusion: There was a significant decrease in neurologically intact discharge with increasing number of epinephrine doses, and our data suggests that seven or more doses of epinephrine is almost always futile. While further prospective studies are needed, clinicians should consider epinephrine doses when weighing the futility or benefit of continued resuscitation efforts.

To explore the effects of solvent-ionomer interactions in catalyst inks on the structure and performance of Cu catalyst layers (CLs) for CO2 electrolysis, we used a “like for like” rationale to select acetone and methanol as dispersion solvents with a distinct affinity for the ionomer backbone or sulfonated ionic heads, respectively, of the perfluorinated sulfonic acid (PFSA) ionomer Aquivion. First, we characterized the morphology and wettability of Aquivion films drop-cast from acetone- and methanol-based inks on flat Cu foils and glassy carbons. On a flat surface, the ionomer films cast from the Aquivion and acetone mixture were more continuous and hydrophobic than films cast from methanol-based inks. Our study’s second stage compared the performance of Cu nanoparticle CLs prepared with acetone and methanol on gas diffusion electrodes (GDEs) in a flow cell electrolyzer. The effects of the ionomer-solvent interaction led to a more uniform and flooding-tolerant GDE when acetone was the dispersion solvent (acetone-CL) than when we used methanol (methanol-CL). As a result, acetone-CL yielded a higher selectivity for CO2 electrolysis to C2+ products at high current density, up to 25% greater than methanol-CL at 500 mA cm-2. Ethylene was the primary product for both CLs, with a Faradaic efficiency for ethylene of 47.4 ± 4.0% on the acetone-CL and that of 37.6 ± 5.5% on the methanol-CL at a current density of 300 mA cm-2. We attribute the enhanced C2+ selectivity of the acetone-CL to this electrode’s better resistance to electrolyte flooding, with zero seepage observed at tested current densities. Our findings reveal the critical role of solvent-ionomer interaction in determining the film structure and hydrophobicity, providing new insights into the CL design for enhanced multicarbon production in high current densities in CO2 electrolysis processes., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ChemE/Materials for Energy Conversion and Storage

In this paper, we present and reflect upon a creative and participatory approach for engaging citizens in imagining desirable “zero”-waste futures that include different values and perspectives. The approach emerged through a 4-month collaboration involving academic researchers and creative professionals and was prototyped in a formerly industrial neighborhood of Utrecht (het Werkspoorkwartier), currently being developed as a creative circular manufacturing area. With our approach, we inquire into and provide an alternative to predominant technology-centered policy visions, which portray the issues of waste as objective challenges that can be addressed through data-driven technological solutions. Such visions neglect many other perspectives and values, particularly those of citizens that face the issue of waste in everyday life, thus providing only a narrow vision of how the future might look like. To gather and articulate different perspectives on alternative “zero”-waste futures, we focus on citizen-science-inspired and speculative design methods to engage people and stimulate imagining futures that bring to light diverse values and perspectives. In the development of the methods, we work in close collaboration with creative practitioners, both in terms of anchoring the research in a real-world context and in terms of combining our different types of expertise. Reflecting on the project, we discuss the potential of our transdisciplinary approach and the co-produced methods to intervene in how we see and imagine alternative futures. We do so by taking “translation” as an analytical lens to understand how different meanings and visions are created through experiential, material, and affective modes of expression. Specifically, we will analyze the translations that occur in the processes of moving from abstract data to matters of concern, and from desirable futures to actionable presents. Looking at these multiple processes through the lens of translation will ser

•Numerous environmental, political, and pandemic factors need remote study •From live streaming and cameras to big data, new and innovative methods •Fusing methods may increase volume, variety, velocity, veracity, value of analysis. •Synthesises & develops the Remote Methods in Leisure Settings Framework •Applies methods to leisure settings, like events & tourist spaces

Nasopulmonary mites (NPMs) of the family Halarachnidae are obligate endoparasites that colonize the respiratory tracts of mammals. NPMs damage surface epithelium resulting in mucosal irritation, respiratory illness, and secondary infection, yet the role of NPMs in facilitating pathogen invasion or dissemination between hosts remains unclear. Using 16S rRNA massively parallel amplicon sequencing of six hypervariable regions (or "16S profiling"), we characterized the bacterial community of NPMs from 4 southern sea otters (Enhydra lutris nereis). This data was paired with detection of a priority pathogen, Streptococcus phocae, from NPMs infesting 16 southern sea otters and 9 California sea lions (Zalophus californianus) using nested conventional polymerase chain reaction (nPCR). The bacteriome of assessed NPMs was dominated by Mycoplasmataceae and Vibrionaceae, but at least 16 organisms with pathogenic potential were detected as well. Importantly, S. phocae was detected in 37% of NPM by nPCR and was also detected by 16S profiling. Detection of multiple organisms with pathogenic potential in or on NPMs suggests they may act as mechanical vectors of bacterial infection for marine mammals.

BACKGROUND: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

BACKGROUND: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. METHODS: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). RESULTS: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. CONCLUSIONS: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter def

In this paper, we propose the concept of controversing as an approach for engaging citizens in debates around the datafied city and in shaping responsible smart cities that incorporate diverse public values. Controversing addresses the engagement of citizens in discussions about the datafication of urban life by productively deploying controversies around data. Attempts to engage citizens in the smart city frequently involve ‘neutral’ data visualisations aimed at making abstract sociotechnical issues more tangible. In addition, citizens are meant to gather around issues already defined externally by others. Instead, we focus on how people might become engaged and develop the capacity to shape alternative urban futures. We suggest that making controversial apparently less contentious issues in the smart city allows people to identify their own issues, come together temporarily as a public, imagine alternative possibilities and thus develop capacities for action. In this context, controversies can act as agents of change and open up new spaces for participation and action. We develop the notion of controversing as a deliberate strategy of making datafication controversial, and operationalise the term along the dimensions of recontextualisation, meaning-making and agency. We then look at two cases from the mid-sized city of Amersfoort in the Netherlands, first to test the conceptual potential of controversing to expose how frictions shape citizen engagement, and second to analyse how controversing may frame design-oriented methods aimed at involving diverse participants in discussing datafication and defining public values in the datafied smart city.

Highlights: • Embracing the idea of Students as Partners as a normal way of working in universities in relation to subject-based research and inquiry can enhance the student experience, help staff balance the different aspects of their jobs and solve problems for external clients. • Subject-based research and inquiry can be undertaken by students at all levels but should always be embedded into their curriculum. • Equality in collaboration is important as it leads to the formation of communities of practice between stakeholders that can continue outside of the original project. These communities are important in terms of creating social networks that create new knowledge or solve problems. • Collaborative opportunities within the context of the Visitor Economy are abundant and can offer solutions to global, national, regional or local challenges.

Mites from the family Halarachnidae Oudemans 1906 are obligate endoparasites that colonize the respiratory tracts of free-living and captive marine mammals. Infestations can range from mild to severe and result in respiratory tract irritation or impairment. Nasopulmonary acariasis was determined to be a contributing cause of death among several southern sea otters Enhydra lutris nereis Merriam 1904 in a longitudinal study of otter mortality, and proximity to Pacific harbor seals Phoca vitulina richardii Gray 1864 was a significant risk factor for sea otter infestation. Beyond scattered opportunistic reports, each halarachnid mite species' affinity for particular hosts and the extent of mite transmission between host species is poorly understood. We investigated the identity and prevalence of nasopulmonary mites from Pacific harbor seals, California sea lions Zalophus californianus Lesson 1828, northern elephant seals Mirounga angustirostris Gill 1866, northern fur seals Callorhinus ursinus Linnaeus 1758, and Guadalupe fur seals Arctocephalus philippii townsendi Merriam 1897 to complement published nasopulmonary mite findings from sympatric southern sea otters during a comparable timeframe. Halarachnid mite infestation was common among California sea lions (74.1%), northern fur seals (73.3%), and northern elephant seals (46.6%), but was less common among harbor seals (18.7%) and Guadalupe fur seals (8.8%). Observed host-mite relationships suggest a distinct host specificity, with genus Orthohalarachne infesting otariids, and genus Halarachne infesting phocids and lutrinids along the California coast. Harbor seals and southern sea otters were the primary hosts of H. halichoeri, but one nothern elephant seal was infested with both H. miroungae and a single H. halichoeri. We also present the first high-resolution SEM images for H. miroungae and O. attenuata and possible evidence for a new host record for H. halichoeri.

With the appearance of digital reading devices, speculations about the end of the printed book emerged (Ballatore & Natale, 2016). Previous studies have tried to address these concerns and approached this phenomenon as a debate between the old and the new version of the book (Martin & Quan-Haase, 2013; van der Velde & Ernst, 2009). This thesis, on the contrary, transcends the belief that digital reading devices will replace printed books. Instead, it focuses on studying the experiences academic users live with these devices by studying the coexistence and complementarity of printed books and digital reading devices. This one, although it had been accepted in previous literature, had not yet been researched. To do so, I addressed the academic segment during the COVID-19 pandemic, as previous literature shows that this global situation has increased the interest in digital reading (Adeyemi, 2020; Parikh et al., 2020). By performing a three-step research approach, this thesis aims to investigate the role of affordances in the reading experience of academic users. Firstly, a survey was distributed to obtain an overview of the current phenomenon and to invite participants to the subsequent step. Secondly, semi-structured interviews were carried out to investigate people’s interactions with the devices. Thirdly, the participants from the interviews were invited to a week of reading during which they documented and described in better detail their experiences with these formats. The obtained information was processed and analysed with affordances as a methodological framework. This research design allowed to study the meaning behind the affordances stated by the participants. It was concluded that academic users use printed books, digital reading devices and their affordances to complete their tasks or to enhance their reading experience. Evidence of affordances being simultaneously used was also found, contributing to a better understanding of the neglected phenomenon of

With the appearance of digital reading devices, speculations about the end of the printed book emerged (Ballatore & Natale, 2016). Previous studies have tried to address these concerns and approached this phenomenon as a debate between the old and the new version of the book (Martin & Quan-Haase, 2013; van der Velde & Ernst, 2009). This thesis, on the contrary, transcends the belief that digital reading devices will replace printed books. Instead, it focuses on studying the experiences academic users live with these devices by studying the coexistence and complementarity of printed books and digital reading devices. This one, although it had been accepted in previous literature, had not yet been researched. To do so, I addressed the academic segment during the COVID-19 pandemic, as previous literature shows that this global situation has increased the interest in digital reading (Adeyemi, 2020; Parikh et al., 2020). By performing a three-step research approach, this thesis aims to investigate the role of affordances in the reading experience of academic users. Firstly, a survey was distributed to obtain an overview of the current phenomenon and to invite participants to the subsequent step. Secondly, semi-structured interviews were carried out to investigate people’s interactions with the devices. Thirdly, the participants from the interviews were invited to a week of reading during which they documented and described in better detail their experiences with these formats. The obtained information was processed and analysed with affordances as a methodological framework. This research design allowed to study the meaning behind the affordances stated by the participants. It was concluded that academic users use printed books, digital reading devices and their affordances to complete their tasks or to enhance their reading experience. Evidence of affordances being simultaneously used was also found, contributing to a better understanding of the neglected phenomenon of

With the appearance of digital reading devices, speculations about the end of the printed book emerged (Ballatore & Natale, 2016). Previous studies have tried to address these concerns and approached this phenomenon as a debate between the old and the new version of the book (Martin & Quan-Haase, 2013; van der Velde & Ernst, 2009). This thesis, on the contrary, transcends the belief that digital reading devices will replace printed books. Instead, it focuses on studying the experiences academic users live with these devices by studying the coexistence and complementarity of printed books and digital reading devices. This one, although it had been accepted in previous literature, had not yet been researched. To do so, I addressed the academic segment during the COVID-19 pandemic, as previous literature shows that this global situation has increased the interest in digital reading (Adeyemi, 2020; Parikh et al., 2020). By performing a three-step research approach, this thesis aims to investigate the role of affordances in the reading experience of academic users. Firstly, a survey was distributed to obtain an overview of the current phenomenon and to invite participants to the subsequent step. Secondly, semi-structured interviews were carried out to investigate people’s interactions with the devices. Thirdly, the participants from the interviews were invited to a week of reading during which they documented and described in better detail their experiences with these formats. The obtained information was processed and analysed with affordances as a methodological framework. This research design allowed to study the meaning behind the affordances stated by the participants. It was concluded that academic users use printed books, digital reading devices and their affordances to complete their tasks or to enhance their reading experience. Evidence of affordances being simultaneously used was also found, contributing to a better understanding of the neglected phenomenon of

AIMS: The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. METHODS AND RESULTS: Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484-0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7. CONCLUSION: In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

ICTs, personal data, digital rights, the GDPR, data privacy, online security… these terms, and the concepts behind them, are increasingly common in our lives. Some of us may be familiar with them, but others are less aware of the growing role of ICTs and data in our lives - and the potential risks this creates. These risks are even more pronounced for vulnerable groups in society. People can be vulnerable in different, often overlapping, ways, which place them at a disadvantage to the majority of citizens; Table 3 in this guide presents some of the many forms and causes of vulnerability. As a result, vulnerable people need greater support to navigate the digital world, and to ensure that they are able to exercise their rights. This guide explains where such support can be found, and also answers the following questions: What are the main ethical and legal issues around ICTs for vulnerable citizens? Who is vulnerable in Europe? How do issues around ICTs affect vulnerable people in particular? This guide is a resource for members of vulnerable groups, people who work with vulnerable groups, and citizens more broadly. It is also useful for data controllers who collect data about vulnerable citizens. While focused on citizens in Europe, it may be of interest to people in other parts of the world. It forms part of the Citizens' Information Pack produced by the PANELFIT project, and is available in English, French, German, Italian and Spanish.

To understand susceptibility of wild California sea lions and Northern elephant seals to influenza A virus (IAV), we developed an ex vivo respiratory explant model and used it to compare infection kinetics for multiple IAV subtypes. We first established the approach using explants from colonized rhesus macaques, a model for human IAV. Trachea, bronchi, and lungs from 11 California sea lions, 2 Northern elephant seals, and 10 rhesus macaques were inoculated within 24 h postmortem with 6 strains representing 4 IAV subtypes. Explants from the 3 species showed similar IAV infection kinetics, with peak viral titers 48 to 72 h post-inoculation that increased by 2 to 4 log10 PFU/explant relative to the inoculum. Immunohistochemistry localized IAV infection to apical epithelial cells. These results demonstrate that respiratory tissue explants from wild marine mammals support IAV infection. In the absence of the ability to perform experimental infections of marine mammals, this ex vivo culture of respiratory tissues mirrors the in vivo environment and serves as a tool to study IAV susceptibility, host range, and tissue tropism. IMPORTANCE Although influenza A virus can infect marine mammals, a dearth of marine mammal cell lines and ethical and logistical challenges prohibiting experimental infections of living marine mammals mean that little is known about IAV infection kinetics in these species. We circumvented these limitations by adapting a respiratory tract explant model first to establish the approach with rhesus macaques and then for use with explants from wild marine mammals euthanized for nonrespiratory medical conditions. We observed that multiple strains representing 4 IAV subtypes infected trachea, bronchi, and lungs of macaques and marine mammals with variable peak titers and kinetics. This ex vivo model can define infection dynamics for IAV in marine mammals. Further, use of explants from animals euthanized for other reasons reduces use of animals in research.

Rio 2016 sought to connect Olympic-tourists with the city’s local-Cariocan community and culture. Yet the way mega-events are spatially and regulatorily organized, alongside the behavioural tendencies of Olympic-tourists, constrain such ambitions. Using Rio 2016 as a case-study, we offer in-depth, qualitative insights through the lens of 35 individual Olympic-tourists to examine how and why these factors determine behaviour, and thus experiences across host-environments. We detail how concerns over tourists’ safety result in managers designing risk averse experiences, produced by overlaying hyper-securitized and regulatory enforcements inside existing tourist bubbles, creating what we refer to as a ‘double bubble’ – reducing the likelihood of visitors venturing ‘off-the-beaten-track’. Whilst Olympic-bubbles protect tourists from outside threats, they restrict cultural engagement with the wider city, neighbourhoods and locals–side-lining other sides to Rio. We suggest managers adopt a dual-strategy of ‘local infusion’ in and ‘tourist diffusion’ beyond official zones to achieve intended goals., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Inherited retinal diseases (IRDs) are a major cause of visual impairment. These clinically heterogeneous disorders are caused by pathogenic variants in more than 270 genes. As 30–40% of cases remain genetically unexplained following conventional genetic testing, we aimed to obtain a genetic diagnosis in an IRD cohort in which the genetic cause was not found using whole-exome sequencing or targeted capture sequencing. We performed whole-genome sequencing (WGS) to identify causative variants in 100 unresolved cases. After initial prioritization, we performed an in-depth interrogation of all noncoding and structural variants in genes when one candidate variant was detected. In addition, functional analysis of putative splice-altering variants was performed using in vitro splice assays. We identified the genetic cause of the disease in 24 patients. Causative coding variants were observed in genes such as ATXN7, CEP78, EYS, FAM161A, and HGSNAT. Gene disrupting structural variants were also detected in ATXN7, PRPF31, and RPGRIP1. In 14 monoallelic cases, we prioritized candidate noncanonical splice sites or deep-intronic variants that were predicted to disrupt the splicing process based on in silico analyses. Of these, seven cases were resolved as they carried pathogenic splice defects. WGS is a powerful tool to identify causative variants residing outside coding regions or heterozygous structural variants. This approach was most efficient in cases with a distinct clinical diagnosis. In addition, in vitro splice assays provide important evidence of the pathogenicity of rare variants.

A distinct ulcerative dermatitis known as “freshwater skin disease” is an emerging clinical and pathological presentation in coastal cetaceans worldwide. In Australia, two remarkably similar mortality events enabled the creation of a case definition based on pathology and environmental factors. The first affected a community of endemic Tursiops australis in the Gippsland Lakes, Victoria, while the second occurred among T. aduncus resident in the Swan-Canning River system, Western Australia. The common features of both events were (1) an abrupt and marked decrease in salinity (from > 30ppt to < 5ppt) due to rainfall in the catchments, with hypo-salinity persisting weeks to months, and (2) dermatitis characterized grossly by patchy skin pallor that progressed to variable circular or targetoid, often raised, and centrally ulcerated lesions covering up to 70% of the body surface. The affected skin was often colonized by a variety of fungal, bacterial and algal species that imparted variable yellow, green or orange discoloration. Histologic lesions consisted of epidermal hydropic change leading to vesiculation and erosion; alternately, or in addition, the formation of intra-epithelial pustules resulting in ulceration and hypodermal necrosis. Thus, the environmental factors and characteristic pathologic lesions, are necessary components of the case definition for freshwater skin disease.

OBJECTIVE:: To identify predictors of epilepsy and clinical relapses in children presenting with acute disseminated encephalomyelitis (ADEM). METHODS:: Children presenting with ADEM between 2005 and 2017 and tested clinically for MOG-Ab were identified from three tertiary paediatric neurology centres in the United Kingdom. Patients were followed up for a median of 6 years (range, 1-16 years). RESULTS:: A total of 74 children were studied (38 females; median age at first presentation: 4.5 years (range, 1.4-16 years)). MOG-Ab was positive in 50/74 (67.6%) of cases, and 27 (54%) of MOG-Ab positive children presented with a neurological relapse over time. MOG-Ab was more frequently positive in the relapsing group than in the monophasic group (27/31 vs 23/43; odds ratio 5.9 (95% CI: 1.8-19.7); p = 0.002). 16/74 (22%) children had seizures during the acute presentation with ADEM and 12/74 (16.2%) patients were diagnosed with post-ADEM epilepsy. The diagnosis of post-ADEM epilepsy was more frequently observed in children with relapsing disease than monophasic disease (10/31 vs 2/43; odds ratio 9.8 (95% confidence interval (CI): 2.0-48.7); p = 0.003), in children who had positive intrathecal oligoclonal bands than those with negative bands (4/7 vs 4/30; odds ratio 8.7 (95% CI: 1.4-54.0); p = 0.027) and in children who had positive MOG-Ab than negative MOG-Ab cases (11/12 vs 39/62; odds ratio 6.5 (95% CI:0.8-53.6); p = 0.051). CONCLUSION:: A higher relapse rate and a greater risk of post-ADEM epilepsy in children with MOG-Ab-associated disease may indicate a chronic disease with immune-mediated seizures in these children.

The aim of this workshop was to ask potential end-users of the citizens’ information pack on legal and ethical issues around ICTs (i.e. citizens and citizens’ groups) the following questions: What is your knowledge of the EU’s General Data Protection Regulation (GDPR), and what actions have you taken in response to these regulations? What challenges are you experiencing in ensuring the protection and security of your project data, and compliance with the GDPR, within existing data management processes/systems? What information/tools/resources do you need to overcome these challenges? What are the best formats/channels for receiving, sharing and acting upon this information? What is the most appropriate structure/format(s) for the citizens’ information pack?

The ability to reproduce the experimental structure of water around the sodium and potassium ions is a key test of the quality of interaction potentials due to the central importance of these ions in a wide range of important phenomena. Here, we simulate the Na+ and K+ ions in bulk water using three density functional theory functionals: (1) the generalized gradient approximation (GGA) based dispersion corrected revised Perdew, Burke, and Ernzerhof functional (revPBE-D3) (2) the recently developed strongly constrained and appropriately normed (SCAN) functional (3) the random phase approximation (RPA) functional for potassium. We compare with experimental X-ray diffraction (XRD) and X-ray absorption fine structure (EXAFS) measurements to demonstrate that SCAN accurately reproduces key structural details of the hydration structure around the sodium and potassium cations, whereas revPBE-D3 fails to do so. However, we show that SCAN provides a worse description of pure water in comparison with revPBE-D3. RPA also shows an improvement for K+, but slow convergence prevents rigorous comparison. Finally, we analyse cluster energetics to show SCAN and RPA have smaller fluctuations of the mean error of ion-water cluster binding energies compared with revPBE-D3.

Navarini and Citroni provide a summary of the relationship between order and liminality, and show how this analytical framework facilitates a better understanding of the consolidation of ‘populist’ political forces and their incorporation in Italy’s government. The authors focus on the campaigning prior to the Italian elections of 2018 and their immediate aftermath, a period when the frameworks of ritual order and liminality overlapped; they draw attention to the emergence of threshold zones of political discourse and practice that gradually moved from the periphery to the ‘symbolic centre’. This process involved subversion of the established rules and changes to the symbols of social ties, such as representations of national cohesion and ‘the other’, that normally affect the reproduction of community power.

Knowing how well higher education providers prepare learners for the working world is becoming increasingly important at all programme levels, and this is nowhere more apparent than with vocational education training. Ensuring our learners can hit the ground running and become immediately productive is essential for the relevance, and probably the survival, of New Zealand’s Institutes of Technology and Polytechnics (ITPs). Yet while there is much commentary about the challenges of transitions from tertiary study into employment and the ‘employability skills gap’, there is all too little given to how this is being addressed in teaching. This paper describes the work of an inter-institutional research collaboration into current approaches being used to embed skills that enhance employability. Drawing on a number of frameworks and models, the research team selected ten core attributes: positive attitude, communication, teamwork, self-management, willingness to learn, thinking skills, resilience, innovation, entrepreneurship and cultural competence. The team then identified a range of strategies being used by highly commended teachers to enhance the ten employability skills: firstly, by observing classroom and online practices of 23 selected teachers from participating organisations; and secondly through follow-up interviews with the same teachers. The key takeaway of this research is raised awareness and intentionality of the overt and covert approaches vocational educators are using to enhance the employability of their students.

Electronic gaming machines (slot machines) contribute to problem gambling in New Zealand and worldwide. Information displays are one harm minimisation feature of New Zealand electronic gaming machines that has been investigated in recent years. New Zealand gamblers see two types of displays: interruptive pop-up displays after a set period of time has passed, and elective displays if a player presses an information button. These displays inform the gambler about their current session with the intention that they will facilitate informed decisions about continuing play or quitting. The current study used a week-long set of electronic gaming machine data from across New Zealand to run an exploratory investigation into the utility of these information displays. We first observed that fewer than 2% of pop-up displays resulted in people quitting. On this basis it is unlikely that interruptive pop-up displays are meaningfully reducing harm. Our analysis also revealed timing differences in how pop-up displays are scheduled on machines produced by different manufacturers. The likelihood of quitting on a pop-up was influenced by complex interactions of machine and session characteristics, however these effects were small. Secondly, our investigation of elective displays also identified a low rate of access, indicating they are also unlikely to be working effectively as a harm minimisation tool. Analysis revealed players’ likelihood of accessing an elective display was mostly influenced by the venue type they were in and the manufacturer of the machine. Possible recommendations to improve both types of displays include changes to message content, scheduled timing and visual features.

The report acknowledges where Lincoln City Football Club (LCFC) is already making a positive contribution to ‘Brand Lincoln’ and the economy, but also seeks to offer suggestions on how they might enhance and develop this for the benefit of the club and the city. The report is exploratory in nature and rather than reporting simply on numerical evidence of impact, which is scant at this point in time and an initial investigation as produced here was required to ascertain which areas to examine, it seeks to consolidate knowledge about the current contribution of LCFC on ‘Brand Lincoln’ and the wider visitor economy and to suggest ways in which this could be enhanced and developed. The report is presented in four sections. The first is a short section to contextualise the research that has taken place. The following two sections are designed to provoke discussion between LCFC’s Executive Management Team and spark ideas about new ways of capitalising on the club’s success and making a positive contribution to the city’s visitor economy. To achieve this we examine the current and potential contribution of LCFC to the city of Lincoln through engaging with cultural programming, leveraging fans, utilising fan zones, and the concept of the last mile in sporting events and venues. We then examine the current and potential economic benefits to the hospitality and leisure sectors in Lincoln, looking at food and beverage outlets and accommodation, and then retail and transportation. Finally we consider the potential for further partnership research between LCFC, The University of Lincoln, and Coventry University, as we believe there is further research potential in this area.

Sophie Duignan,1,2 Sarah L Doyle,2 Colin J McMahon1,2 1Department of Paediatric Cardiology, Our Lady’s Children’s Hospital, Dublin 12, Ireland; 2Department of Immunology, National Children’s Research Centre, Dublin, IrelandCorrespondence: Colin J McMahonDepartment of Paediatric Cardiology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, IrelandTel +3 531 428 2854Fax +3 531 409 6181Email cmcmahon992004@yahoo.comAbstract: Kawasaki disease (KD), an acute, self-limiting, medium-sized arterial vasculitis, is now the most common cause of acquired heart disease in childhood in the developed world. In this review, we discuss the diagnosis of KD, predicting resistance to traditional therapy and treatment options in refractory or high-risk disease. We also highlight ongoing clinical trials and other potential avenues of research which may prove beneficial in managing children, especially those with resistant KD.Keywords: aneurysm, arteritis, coronary, inflammation, Kawasaki, vasculitis

Unsupported non-bridged uranium-carbon double bonds have long been sought after in actinide chemistry as fundamental synthetic targets in the study of actinide-ligand multiple bonding. Here we report that, utilizing Ih(7)-C80 fullerenes as nanocontainers, a diuranium carbide cluster, U=C=U, has been encapsulated and stabilized in the form of UCU@Ih(7)-C80. This endohedral fullerene was prepared utilizing the Krätschmer-Huffman arc discharge method, and was then co-crystallized with nickel(II) octaethylporphyrin (NiII-OEP) to produce UCU@Ih(7)-C80·[NiII-OEP] as single crystals. X-ray diffraction analysis reveals a cage-stabilized, carbide-bridged, bent UCU cluster with unexpectedly short uranium-carbon distances (2.03 Å) indicative of covalent U=C double-bond character. The quantum-chemical results suggest that both U atoms in the UCU unit have formal oxidation state of +5. The structural features of UCU@Ih(7)-C80 and the covalent nature of the U(f1)=C double bonds were further affirmed through various spectroscopic and theoretical analyses.

AIM: Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. METHOD: Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). INTERPRETATION: Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion t

In this work we prepare Langmuir–Blodgett monolayers with a trifunctional amphiphilic anthraphane monomer. Upon spreading at the air/water interface, the monomers self-assemble into 1 nm-thin monolayer islands, which are highly fluorescent and can be visualized by the naked eye upon excitation. In situ fluorescence spectroscopy indicates that in the monolayers, all the anthracene units of the monomers are stacked face-to-face forming excimer pairs, whereas at the edges of the monolayers, free anthracenes are present acting as edge groups. Irradiation of the monolayer triggers [4 + 4]-cycloadditions among the excimer pairs, effectively resulting in a two-dimensional (2D) polymerization. The polymerization reaction also completely quenches the fluorescence, allowing to draw patterns on the monomer monolayers. More interestingly, after transferring the monomer monolayer on a solid substrate, by employing masks or the laser of a confocal scanning microscope, it is possible to arbitrarily select the parts of the monolayer that one wants to polymerize. The unpolymerized regions can then be washed away from the substrate, leaving 2D macromolecular monolayer objects of the desired shape. This photolithographic process employs 2D polymerizations and affords 1 nm-thin coatings.

Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100% potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95% CI: 1.025-1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95% confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95% CI: 0.871-1.432), corresponding to an absolute potency of 36,238 IU/mg (95% CI: 28,308-46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulte

First principles molecular dynamics simulation protocol is established using revised functional of Perdew-Burke-Ernzerhof (revPBE) in conjunction with Grimme's third generation of dispersion (D3) correction to describe the properties of water at ambient conditions. This study also demonstrates the consistency of the structure of water across both isobaric (NpT) and isothermal (NVT) ensembles. Going beyond the standard structural benchmarks for liquid water, we compute properties that are connected to both local structure and mass density fluctuations that are related to concepts of solvation and hydrophobicity. We directly compare our revPBE results to the Becke-Lee-Yang-Parr (BLYP) plus Grimme dispersion corrections (D2) and both the empirical fixed charged model (SPC/E) and many body interaction potential model (MB-pol) to further our understanding of how the computed properties herein depend on the form of the interaction potential.

A theoretical model of haemoglobin is presented to explain an anomalous cationic Hofmeister effect observed in protein aggregation. The model quantifies competing proposed mechanisms of non-electrostatic physisorption and chemisorption. Non-electrostatic physisorption is stronger for larger, more polarizable ions with a Hofmeister series Li+ > K+ > Cs+. Chemisorption at carboxylate groups is stronger for smaller kosmotropic ions, with the reverse series Li+ > K+ > Cs+. We assess aggregation using second virial coefficients calculated from theoretical protein-protein interaction energies. Taking Cs+ to not chemisorb, comparison with experiment yields mildly repulsive cation-carboxylate binding energies of 0.48 kBT for Li+ and 3.0 kBT for K+. Aggregation behaviour is predominantly controlled by short-range protein interactions. Overall, adsorption of the K+ ion in the middle of the Hofmeister series is stronger than ions at either extreme since it includes contributions from both physisorption and chemisorption. This results in stronger attractive forces and greater aggregation with K+, leading to the non-conventional Hofmeister series K+ > Cs+ ≈ Li+.