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A history of high-power laser research and development in the United Kingdom
No full textThe first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years
Cohort profile: DOLORisk Dundee: a longitudinal study of chronic neuropathic pain
No full textPurpose Neuropathic pain is a common disorder of the somatosensory system that affects 7%–10% of the general population. The disorder places a large social and economic burden on patients as well as healthcare services. However, not everyone with a relevant underlying aetiology develops corresponding pain. DOLORisk Dundee, a European Union-funded cohort, part of the multicentre DOLORisk consortium, was set up to increase current understanding of this variation in onset. In particular, the cohort will allow exploration of psychosocial, clinical and genetic predictors of neuropathic pain onset.
Participants DOLORisk Dundee has been constructed by rephenotyping two pre-existing Scottish population cohorts for neuropathic pain using a standardised ‘core’ study protocol: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) (n=5236) consisting of predominantly type 2 diabetics from the Tayside region, and Generation Scotland: Scottish Family Health Study (GS:SFHS; n=20 221). Rephenotyping was conducted in two phases: a baseline postal survey and a combined postal and online follow-up survey. DOLORisk Dundee consists of 9155 participants (GoDARTS=1915; GS:SFHS=7240) who responded to the baseline survey, of which 6338 (69.2%; GoDARTS=1046; GS:SFHS=5292) also responded to the follow-up survey (18 months later).
Findings to date At baseline, the proportion of those with chronic neuropathic pain (Douleur Neuropathique en 4 Questions questionnaire score ≥3, duration ≥3 months) was 30.5% in GoDARTS and 14.2% in Generation Scotland. Electronic record linkage enables large scale genetic association studies to be conducted and risk models have been constructed for neuropathic pain.
Future plans The cohort is being maintained by an access committee, through which collaborations are encouraged. Details of how to do this will be available on the study website (http://dolorisk.eu/). Further follow-up surveys of the cohort are planned and funding applications are being prepared to this effect. This will be conducted in harmony with similar pain rephenotyping of UK Biobank
The changing landscape of the vulnerable plaque: a call for fine-tuning of preclinical models
No full textFor decades, the pathological definition of the vulnerable plaque led to invaluable insights into the mechanisms that underlie myocardial infarction and stroke. Beyond plaque rupture, other mechanisms, such as erosion, may elicit thrombotic events underlining the complexity and diversity of the atherosclerotic disease. Novel insights, based on single-cell transcriptomics and other “omics” methods, provide tremendous opportunities in the ongoing search for cell-specific determinants that will fine-tune the description of the thrombosis prone lesion. It coincides with an increasing awareness that knowledge on lesion characteristics, cell plasticity and clinical presentation of ischemic cardiovascular events have shifted over the past decades. This shift correlates with an observed changes of cell composition towards phenotypical stabilizing of human plaques. These stabilization features and mechanisms are directly mediated by the cells present in plaques and can be mimicked in vitro via primary plaque cells derived from human atherosclerotic tissues.
In addition, the rapidly evolving of sequencing technologies identify many candidate genes and molecular mechanisms that may influence the risk of developing an atherosclerotic thrombotic event - which bring the next challenge in sharp focus: how to translate these cell-specific insights into tangible functional and translational discoveries
Epidemiological data and genome sequencing reveals that nosocomial transmission of SARS-CoV-2 is underestimated and mostly mediated by a small number of highly infectious individuals
No full textObjectives: Despite robust efforts, patients and staff acquire SARS-CoV-2 infection in hospitals. We investigated whether whole-genome sequencing enhanced the epidemiological investigation of healthcare-associated SARS-CoV-2 acquisition.
Methods: From 17-November-2020 to 5-January-2021, 803 inpatients and 329 staff were diagnosed with SARS-CoV-2 infection at four Oxfordshire hospitals. We classified cases using epidemiological definitions, looked for a potential source for each nosocomial infection, and evaluated genomic evidence supporting transmission.
Results: Using national epidemiological definitions, 109/803(14%) inpatient infections were classified as definite/probable nosocomial, 615(77%) as community-acquired and 79(10%) as indeterminate. There was strong epidemiological evidence to support definite/probable cases as nosocomial. Many indeterminate cases were likely infected in hospital: 53/79(67%) had a prior-negative PCR and 75(95%) contact with a potential source. 89/615(11% of all 803 patients) with apparent community-onset had a recent hospital exposure. Within 764 samples sequenced 607 genomic clusters were identified (>1 SNP distinct). Only 43/607(7%) clusters contained evidence of onward transmission (subsequent cases within ≤ 1 SNP). 20/21 epidemiologically-identified outbreaks contained multiple genomic introductions. Most (80%) nosocomial acquisition occurred in rapid super-spreading events in settings with a mix of COVID-19 and non-COVID-19 patients.
Conclusions: Current surveillance definitions underestimate nosocomial acquisition. Most nosocomial transmission occurs from a relatively limited number of highly infectious individuals
The ethics of shared Covid-19 risks: an epistemological framework for ethical health technology assessment of risk in vaccine supply chain infrastructures
No full textThis article addresses the topic of shared responsibilities in supply chains, with a specific focus on the application of the Internet of Things (IoT) in e-health environments, and Industry 4.0 issues - concerning data security, privacy, reliability and management, data mining and knowledge exchange as well as health prevention. In this article, we critically review methodologies and guidelines that have been proposed to approach these ethical aspects in digital supply chain settings. The emerging framework presents new findings on how digital technologies affect vaccine shared supply chain systems. Through epistemological analysis, the article derives new insights for transparency and accountability of supply chain cyber risk from Internet of Things systems. This research devises a framework for ethical awareness, assessment, transparency and accountability of the emerging cyber risk from integrating IoT technologies on shared Covid-19 healthcare supply chain infrastructure
Material and charge transport of large organic salt clusters and nanoparticles in electrospray ion beam deposition
No full textElectrospray ion beam deposition (ES-IBD) or ion soft landing has been demonstrated as a technique suitable for processing nonvolatile molecules in vacuum under perfectly controlled conditions, an approach also desirable for the deposition of nanoparticles. Here, we present results from several approaches to generate, characterize, and deposit nanoparticle ion beams in vacuum for deposition. We focus on cluster ion beams generated by ESI of organic salt solutions. Small cluster ions of the salts appear in the mass spectra as defined peaks. In addition, we find nanoparticle-sized aggregates, appearing as a low intensity background at high m/z-ratio, and show by IBD experiments that these clusters carry the major amount of material in the ion beam. This transition from clusters to nanoparticles, and their successful deposition, shows that ES-IBD can in principle handle ion beams of very heavy and highly charged nanoparticles. In related experiments, however, we found the deposition of nanoparticles from dispersions to be of low reproducibility, due to the lack of control by mass spectrometry
Experimenting with international commercial dispute resolution
No full textIn this essay, we describe the overlapping phenomena of new legal hubs (NLHs), international commercial courts, and arbitral courts. We survey their impact on the law and geopolitics of international commercial dispute resolution, identifying key issues these new dispute resolution institutions raise. While the rise of international commercial courts spans authoritarian and liberal states, Western and Asian states, common law and civil law traditions, it also highlights and builds upon regional differences. We question the assumption that the establishment of new courts is always consistent with an increase in the rule of law, particularly in non-democratic states. We close with thoughts about the potential influence and future role of these institutions. Some of the procedural innovations discussed here may lead to shifts in international commercial dispute resolution for years to come, but the question of whether there is sufficient demand for these new institutions lingers
Exposure of the oesophagus in breast cancer radiotherapy: a systematic review of oesophagus doses published 2010-2020
No full textBackground and Purpose: Breast cancer radiotherapy can increase the risk of subsequent primary oesophageal cancer, with risk increasing according to oesophagus radiation dose. We describe oesophagus exposure from modern breast cancer regimens and discuss the risks of oesophageal cancer for women irradiated recently.
Materials and Methods: A systematic review was undertaken of oesophagus doses from breast cancer radiotherapy regimens published during 2010-2020. Mean and maximum oesophagus doses were described for different target regions irradiated and different radiotherapy techniques.
Results: In 112 published regimens from 18 countries, oesophagus doses varied with target region. For partial breast irradiation, average mean oesophagus dose was 0.2 Gy (range 0.1-0.4) in four regimens; maximum dose was not reported. For breast or chest wall radiotherapy, average oesophagus doses were mean 1.8 Gy (range 0.1-10.4) in 24 regimens and maximum 6.7 Gy (range 0.4-14.3) in seven regimens. For radiotherapy including a nodal region, average oesophagus doses were higher: mean 11.4 Gy (range 1.1-29.3) in 61 regimens and maximum 34.4 Gy (range 3.4-51.3) in 55 regimens. Average mean oesophagus doses were >10 Gy for intensity modulated nodal radiotherapy, but lower for other node techniques.
Conclusions: Mean oesophagus doses from partial breast and breast/chest wall regimens were usually less than 2 Gy, hence radiation-risks will be very small. However, for radiotherapy including lymph nodes, average mean oesophagus dose of 11.4 Gy may nearly double oesophageal cancer risk. Consideration of oesophageal exposure during nodal radiotherapy planning may reduce the risks of radiation-related oesophageal cancer for women irradiated today
Dispute inflation
No full textMuch work has examined the phenomenon of dispute escalation, whereby the concrete measures state actors take edge them closer to war. Less attention has been devoted to the ways in which state actors’ perceptions of what is at stake in a dispute can also change, with important consequences for the likelihood of conflict. This paper examines the phenomenon of dispute inflation – wherein a contest over an object or issue assumes ever greater stakes and significance for its protagonists – and identifies three different mechanisms that can generate increasing non-material stakes. The upshot is that theoretically even a minor dispute can grow into a major conflict due to swelling stakes, especially when dispute inflation spirals. To illustrate these dynamics at work, this paper looks to recent developments in the dispute between the People’s Republic of China and Japan over the Senkaku/Diaoyu Islands