The Situated Self: identity in a world of ambient intelligence

De centrale onderzoeksvraag van deze dissertatie is ‘Heeft Ambient Intelligence invloed op menselijke identiteit, en als dat zo is, waar bestaat die invloed dan uit?’ Deze onderzoeksvraag roept onmiddellijk twee andere vragen op: ‘wat is Ambient Intelligence?’, en ‘wat versta je onder ‘menselijke identiteit’?’ Na een algemene inleiding in hoofdstuk 1, heb ik in hoofdstuk 2 en 3 van deze dissertatie de begrippen ‘Ambient Intelligence’ en ‘identiteit’ tegen het licht gehouden. In het daarna volgende deel, bestaande uit hoofdstuk 4 tot en met 6, kon ik vervolgens de onderzoeksvraag beantwoorden. Ambient Intelligence, zo laat ik in het hoofdstuk 2 van deze dissertatie zien, is een visie op de technologische toekomst, die oorspronkelijk ontwikkeld is door het Nederlandse Philips. Al vrij snel na haar lancering werd deze visie opgepikt door de Europese Commissie en zo is zij uitgegroeid tot een belangrijk onderdeel van de beleidsagenda van de Europese Unie. In een wereld van Ambient Intelligence, zo stelt deze visie, zijn we omringd door netwerken van technologie die aan het zicht onttrokken zijn – weggewerkt in meubels, in muren en ramen, in huishoudelijke en kantoorobjecten, en in kleding of zelfs onze lichamen

Governing Cyberspace: Behavior, Power and Diplomacy

Cyber norms and other ways to regulate responsible state behavior in cyberspace is a fast-moving political and diplomatic field. The academic study of these processes is varied and interdisciplinary, but much of the literature has been organized according to discipline. Seeking to cross disciplinary boundaries, this timely book brings together researchers in fields ranging from international law, international relations, and political science to business studies and philosophy to explore the theme of responsible state behavior in cyberspace. . Divided into three parts, Governing Cyberspace first looks at current debates in and about international law and diplomacy in cyberspace. How does international law regulate state behaviour and what are its limits? How do cyber superpowers like China and Russia shape their foreign policy in relation to cyberspace? The second focuses on power and governance. What is the role for international organisations like NATO or for substate actors like intelligence agencies? How do they adapt to the realities of cyberspace and digital conflict? How does the classic balance of power play out in cyberspace and how do different states position themselves? The third part takes a critical look at multistakeholder and corporate diplomacy. How do global tech companies shape their role as norm entrepreneurs in cyberspace, and how do their cyber diplomatic efforts relate to their corporate identity

Extracranial Trigger Site Surgery for Migraine

Introduction: The headache phase of migraine could in selected cases potentially be treated by surgical decompression of one or more “trigger sites,” located at frontal, temporal, nasal, and occipital sites. This systematic review with subsequent meta-analysis aims at critically evaluating the currently available evidence for the surgical treatment of migraine headache and to determine the effect size of this treatment in a specific patient population. Methods: This study was conducted following the PRISMA guidelines. An online database search was performed. Inclusion was based on studies published between 2000 and March 2018, containing a diagnosis of migraine in compliance with the classification of the International Headache Society. The treatment must consist of one or more surgical procedures involving the extracranial nerves and/or arteries with outcome data available at minimum 6 months. Results: Eight hundred and forty-seven records were identified after duplicates were removed, 44 full text articles were assessed and 14 records were selected for inclusion. A total number of 627 patients were included in the analysis. A proportion of 0.38 of patients (random effects model, 95% CI [0.30–0.46]) experienced elimination of migraine headaches at 6–12 months follow-up. Using data from three randomized controlled trials, the calculated odds ratio for 90–100% elimination of migraine headaches is 21.46 (random effects model, 95% CI [5.64–81.58]) for patients receiving migraine surgery compared to sham or no surgery. Conclusions: Migraine surgery leads to elimination of migraine headaches in 38% of the migraine patients included in this review. However, more elaborate randomized trials are needed with transparent reporting of patient selection, medication use, and surgical procedures and implementing detailed and longer follow-up times

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303