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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

Highlights • PCR.Ai is an automated final interpretation/verification step for in-house qPCR tests. • PCR.Ai was compared to our routine analysis method. • PCR.Ai was accurate for respiratory virus and norovirus detection. • There were significant savings with PCR.Ai. • PCR.Ai is a highly accurate time-saving tool for qPCR analysis., Background We undertook a prospective clinical study to evaluate PCR.Ai’s (www.pcr.ai) accuracy and impact when automating the manual data-analysis and quality control steps associated with routine clinical pathogen testing using real-time PCR (qPCR). Objectives We evaluated the impact of PCR.Ai when used as the final interpretation/verification step for routine in-house qPCR tests for respiratory pathogens and for norovirus for a total of 22,200 interpretations. Study Design We compared PCR.Ai to our existing manual interpretation, to determine accuracy and hands-on time savings. PCR.Ai was accurate. Results and Conclusions There was 100% concurrence between validated respiratory virus and norovirus detection by our manual routine analysis method and PCR.Ai. Furthermore, there were significant routine savings with PCR.Ai of 45 min/respiratory run and 32 min/norovirus run. Our conclusion is that PCR.Ai is a highly accurate time-saving tool that reduces complexity of qPCR analysis and hence the need for specialists and hands-on time. It demonstrated capabilities to enable us to get results out more quickly with lower costs and less risk of errors.

ObjectivesPatients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium.MethodsWe combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations.ResultsOf 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated.ConclusionsNear-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.

Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. Methods: Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. Results: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC50 compared to wildtype. Conclusion: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.

The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It was first introduced into Scotland in February 2020 associated with returning travellers and visitors. By March it was circulating in communities across the UK, and to control COVID-19 cases, and prevent overwhelming of the National Health Service (NHS), a ‘lockdown’ was introduced on 23rd March 2020 with a restriction of people’s movements. To augment the public health efforts a large-scale genome epidemiology effort (as part of the COVID-19 Genomics UK (COG-UK) consortium) resulted in the sequencing of over 5000 SARS-CoV-2 genomes by 18th August 2020 from Scottish cases, about a quarter of the estimated number of cases at that time. Here we quantify the geographical origins of the first wave introductions into Scotland from abroad and other UK regions, the spread of these SARS-CoV-2 lineages to different regions within Scotland (defined at the level of NHS Health Board) and the effect of lockdown on virus ‘success’. We estimate that approximately 300 introductions seeded lineages in Scotland, with around 25% of these lineages composed of more than five viruses, but by June circulating lineages were reduced to low levels, in line with low numbers of recorded positive cases. Lockdown was, thus, associated with a dramatic reduction in infection numbers and the extinguishing of most virus lineages. Unfortunately since the summer cases have been rising in Scotland in a second wave, with >1000 people testing positive on a daily basis, and hospitalisation of COVID-19 cases on the rise again. Examining the available Scottish genome data from the second wave, and comparing it to the first wave, we find that while some UK lineages have persisted through the summer, the majority of lineages responsible for the second wave are new introductions from outside of Scotland and many from outside of the UK. This indicates that, while lockdown in Scotland is directly linked with the first wave case numbers being brought under control, travel-associated imports (mostly from Europe or other parts of the UK) following the easing of lockdown are responsible for seeding the current epidemic population. This demonstrates that the impact of stringent public health measures can be compromised if following this, movements from regions of high to low prevalence are not minimised.

Background Non-specific amplification can arise in real-time PCR when temperatures are above 4 °C during PCR set up. Pressure of high throughput tests, particularly in a clinical setting, can lead to short cuts being taken during PCR set up. Objectives This study set out to evaluate the outcome of exposing a real-time PCR assay to increasing durations of room temperature prior to PCR amplification. Study design A real-time PCR assay was exposed to increasing durations of room temperature prior to PCR amplification. Results We found that reactions left at room temperature for 30 min or more produced non-specific traces in the negative controls which could be mistaken for weak positive traces. In addition we found that the fluorescence of positive control traces was significantly reduced indicating reduced reaction efficiency, however the Ct valves were comparable between all reactions highlighting that control Ct monitoring alone would not have detected this issue. Conclusions This study acts as a reminder for PCR users to set up reactions on ice/chill blocks prior to PCR amplification.

Background Hepatitis C (HCV) NS5A resistance associated amino-acid substitutions (RAS) can exist at baseline in treatment naive individuals and have been shown to be associated with lower rates of sustained virological response (SVR) for patients infected with HCV genotype 1A (G1A) following treatment with NS5A inhibitors. Objectives The aim of this study was to measure the prevalence of baseline NS5A resistance in Scotland. Study design The study population consisted of 531 treatment naive, G1A infected patients. The patient samples were collected between March and September 2017. The NS5A region was amplified and sequenced. Results Baseline NS5A resistance in Scotland is high (16.8%) and is comparable to rates reported by a number of previously published studies. The high rate of baseline RAS, together with the high cost of direct-acting antivirals (DAAs), supports resistance testing to guide current patient treatment. However, given the rate at which new DAAs are currently being licensed with ever broader genotype efficacy and higher SVR rates, baseline resistance testing may not be required in the near future. Conclusions Baseline NS5A inhibitor resistance is high. The results of the present study support performing resistance testing at baseline for current regimens.

Genetic surveillance of seasonal influenza is largely focused upon sequencing of the haemagglutinin gene. Consequently, our understanding of the contribution of the remaining seven gene segments to the evolution and epidemiological dynamics of seasonal influenza is relatively limited. The increased availability of next generation sequencing technologies allows rapid and economic whole genome sequencing (WGS). Here, 150 influenza A(H3N2) positive clinical specimens with linked epidemiological data, from the 2014/15 season in Scotland, were sequenced directly using both Sanger sequencing of the HA1 region and WGS using the Illumina MiSeq platform. Sequences generated by both methods were highly consistent and WGS provided on average >90% whole genome coverage. As reported in other European countries during 2014/15, all strains belonged to genetic group 3C, with subgroup 3C.2a predominating. Inter-subgroup reassortants were identified (9%), including three 3C.3 viruses descended from a single reassortment event, which had persisted in the population. Significant phylogenetic associations with cases of severe acute respiratory illness observed herein warrant further investigation. Severe cases were also more likely to be associated with reassortant viruses (odds ratio: 4.4 (1.3-15.5)) and occur later in the season. These results suggest that increased levels of WGS, linked to clinical and epidemiological data, could improve influenza surveillance.

Background and aims The majority of influenza infections during the 2012/2013 influenza season in Scotland have been due to influenza A H3N2. We report an outbreak of influenza A H3N2 in a vaccinated population of adults in the Regional Virology Laboratory in Glasgow. This investigation was carried out to confirm the epidemiological link between cases. Methods and results Staff with clinical symptoms of influenza-like illness were included. Samples were tested by real-time polymerase chain reaction and sequencing. Staff were interviewed to obtain information regarding symptom onset and vaccination status. Eight confirmed cases and six clinically diagnosed cases were reported, which all occurred within 4 days of a lunchtime Christmas quiz. The eight samples subtyped as H3 virus. The haemagglutinin gene in the confirmed cases was sequenced and shown to be identical. Most of the attendees had been immunised against influenza with the same vaccine batch at least 6 weeks earlier. Conclusion This outbreak appears to have been an isolated incident, which arose due to a social event that provided the ideal conditions for transmission of a respiratory disease. It may have been compounded by low-vaccine effectiveness this season. Sequence data supported the epidemiological link.

Background Transmitted integrase inhibitor resistance is rare, with only a small number of cases reported world-wide to date. Objectives The aim of this study was to assess whether transmitted integrase inhibitor resistance has occurred in Scotland and if so, could there be a case for performing genotypic integrase resistance testing at baseline. Study design The study population consisted of 106 treatment naive, newly diagnosed, HIV positive patients. The patient samples were collected between October 2015 and March 2016 at the time of HIV diagnosis and prior to initiation of anti-retroviral therapy. The integrase region was amplified and sequenced. Results We detected integrase inhibitor resistance (T66I/T) at baseline in one patient sample. This is a non-polymorphic mutation seen in patients receiving elvitegravir which confers high-level resistance to elvitegravir and intermediate resistance to raltegravir. A further 10 patients had accessory mutations which have minimal or no effect on susceptibility to integrase inhibitors. Conclusions Transmitted integrase inhibitor resistance remains rare. The results of the present study do not support performing integrase resistance testing at baseline.

In 1987, following a period of increasing judicial activity, Margaret Brazier published her insightful article on the legal regulation of consent: Patient autonomy and consent to treatment: the role of the law? In her article, she exposed the flaws in the law following the House of Lords case of Sidaway. She considered the strengths and weaknesses of the alternative standards of disclosure: the professional or Bolam standard, the reasonable patient standard, and the particular patient standard. After noting that all of these standards have their problems, she suggested that the best way forward was for a national law and ethics commission to explore the issues before revising the law by legislation. Almost a quarter of a century following her article, Professor Brazier's criticisms remain aposite. In this article, I explain her view of the law in 1987 and then I examine the current law through the lens of her article and conclude that her recommendations still have strength.

Influenza A H1N1 (2009) was declared by the World Health Organisation (WHO) as the first influenza pandemic of the 21st century. Rapid detection of influenza A and differentiation of influenza A H1N1 (2009) and seasonal influenza A is beneficial. In addition the rapid detection of antiviral resistant strains of influenza A H1N1 (2009) would be useful for clinicians to allow for change to an effective treatment at a much earlier stage if resistance is found. It was the aim of this study to develop a real-time RT-PCR that can detect all influenza A viruses and type simultaneously for influenza A H1N1 (2009) and oseltamivir resistant (H275Y) influenza A H1N1 (2009). This multiplex assay will allow laboratories to screen respiratory samples for all types of influenza A, influenza A H1N1 (2009) virus and oseltamivir resistant (H275Y) influenza A H1N1 (2009) virus in a rapid and cost effective format, ensuring that typing methods for seasonal and avian viruses are used on a smaller subset of samples. Since most virology laboratories already offer a molecular service for influenza A this assay could easily be implemented into most areas at little cost therefore increasing local access to resistance testing.

Background A novel influenza A virus, subtype H1N1 of swine-lineage (H1N1 swl) has transmitted rapidly to many regions of the world with evidence of sustained transmission within some countries. Rapid detection and differentiation from seasonal influenza is essential to instigate appropriate patient and public health management and for disease surveillance. Objectives To develop a rapid and sensitive real-time reverse transcriptase polymerase chain reaction (rtRT-PCR) for confirmation of H1N1 swl. Study design A one-step rtRT-PCR approach was employed to target the matrix gene of the novel influenza A/H1N1 swl and validated against a panel of seasonal influenza A (H1N1 and H3N2), swine influenza A/H1N1 and avian influenza A/H5N1 viruses. The assay following validation was then used prospectively to detect H1N1 swl positive specimens from the recent outbreaks in the UK and the Republic of Ireland. Results The one-step H1N1 swl matrix rtRT-PCR successfully detected H1N1 swl clinical specimens and did not cross-react with seasonal influenza A, subtypes H1N1 and H3N2 viruses and swine influenza A (H1N1). The H1N1 swl matrix assay did cross react with H5N1. The H1N1 swl matrix assay was then compared to two other assays using a dilution series and a panel of untyped influenza A positive clinical samples. These experiments found the assay to have a comparable sensitivity to the established universal influenza A rtRT-PCR and was more sensitive than the H1N1 swl specific assay that targeted the H1 region. Conclusions The results demonstrate that the rtRT-PCR is sensitive and should be used alongside existing universal influenza A assays to rapidly detect the novel H1N1 swl virus.

The law in England allows that both parents and competent minors concurrently have the right to consent to medical treatment of the minor. This means that while competent minors may consent to treatment their refusal of consent does not act as an effective veto of treatment and treatment remains lawful if given with parental consent. This approach has been heavily criticized as inconsistent with the House of Lords decision in the Gillick case and damned as ‘palpable nonsense’. In this article, I examine these criticisms and conclude that, far from being illogical, it is entirely consistent with the essential asymmetry between consent to treatment and refusal of treatment. I examine the two metaphors of keyholders and flak jackets used to explain this approach and I suggest that both have value but only when used in combination. I also explain why, contrary to the criticism, it is consistent with Gillick.

Since we are generally not required to act altruistically, one question that arises is may children or incompetent adults be permitted – or required – to act for the benefit of others where the law would ordinarily only permit such an act if it were justified by a valid consent? In this article I consider how the law regulates decision making for children and incompetent adults and whether acts that would otherwise be considered altruistic are permissible. Using organ donation as an example I argue that the law does permit them but only by manipulating the ‘best interests’ test. I consider some of the arguments in favour of allowing such decisions and conclude that it is apparent that there are circumstances in which they should be permitted but that the best interests test is inadequate and dishonestly conceals the real justifications for the decision.

For each month between January 2005 and August 2006, a representative number of outbreaks was examined using nucleic acid sequence analysis. Using this method, we showed that an increase in norovirus activity coincided with the emergence of a new GII genotype 4 variant, which by March 2006 was detected in the majority of health boards in Scotland.

To the editor: Since late 2012, Scotland has seen a significant increase in norovirus activity and the norovirus season began earlier than usual [1]. The article by van Beek et al. published in last week’s issue of Eurosurveillance described the emergence of a new variant of norovirus GII.4 (Sydney strain) in a number of countries [2]. To examine whether this was also the case in Scotland, we examined representative samples from norovirus outbreaks in hospitals submitted to the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow between 8 and 20 November 2012. This time period was chosen as it was after the point when the increased norovirus activity was first reported by Health Protection Scotland [1].

In Chapter 1 I considered the concept of autonomy, which through its relationship to agency may be seen as the driving force of consent. However, autonomy is not the sole guiding principle. In this chapter, I will examine other moral principles and approaches that may be relevant to determining how the law should regulate consent to medical treatment. Rather than attempt to provide a complete model of how the different concerns interact I will in this chapter focus on the relevance of beneficence, justice and virtue in order to provide sufficient background to enable the subsequent development of a more textured model. I have little to say about the principle of non-maleficence, the essence of which is to do no harm. As Szasz noted, this is – if taken too literally – ‘an absurd’ prescription. Much of what the professional does necessarily risks or causes harm and the obligation is, if interpreted literally, an impossible one. It makes better sense to consider the obligation in tandem with the duty of beneficence. An alternative approach is to use a normative concept of harm that requires the act to be both harmful and wrong. Most of the specific duties that arise from this, such as the obligations not to kill, cause injury or pain are relevant only in so far as consent provides the necessary justification to prevent the act being wrongful.

Alasdair Maclean analyses the ethical basis for consent to medical treatment, providing both an extensive reconsideration of the ethical issues and a detailed examination of English law. Importantly, the analysis is given a context by situating consent at the centre of the healthcare professional-patient relationship. This allows the development of a relational model that balances the agency of the two parties with their obligations that arise from that relationship. That relational model is then used to critique the current legal regulation of consent. To conclude, Alasdair Maclean considers the future development of the law and contrasts the model of relational consent with Neil Manson and Onora O'Neill's recent proposal for a model of genuine consent.

A model must incorporate respect for the personhood and self-determination of the patient and should enhance dialogue between the two parties of the relationship. P. G. Smith and L. H. Newton, ‘Physician and patient’ (1984) Consent is not unique to healthcare and, while it may serve parallel functions in different contexts, the regulation of consent should be sensitive to the setting. For example, the requirements for a valid consent in the context of non-commercial sexual relationships are influenced by the necessary absence of formality, which is not the case for consent to healthcare interventions. Furthermore, because consent must always involve at least two agents it is not a free-floating device that can exist in the absence of a relationship. The way healthcare professionals approach consent indicates their attitude towards their patients, which should reflect a moral sensitivity to the issues discussed in the first two chapters, and is central to the relationship between them and their patients. The patient's role in the relationship is equally important and the way in which the patient approaches consent will impact on the effectiveness of the communicative process and the consent decision that results. Thus, it is important to situate consent within the context of the relationship between the patient and the healthcare professional. Positing consent as central to the professional–patient relationship emphasises its communal aspect.

The paper, the opening address to the Conference on Management Training for Scientists and Technologists held at Manchester in July 1986, deals with the problems which must be solved by UK industry if it is to survive in the industrial jungle of the next century. The author sees the most serious cause for concern as being the poor communication between top managements and technologists, originating in and aggravated by historically based cultural and social divisions inside UK society. The first and essential step towards a solution is for top managements to accept that technological change is inevitable and that it will affect their own operations. They must therefore accept the need to continuously review and undertake the replacement of the firm's process, product and management technologies, along with a parallel review and refurbishment of workforce skills. This implies re-education both of the firm's technical arm, including its R&D personnel and, most importantly, of the non-R&D functions which commission R&D and use its results. The author sees functional demarcation lines as a particular evil. He also deplores the preference of UK financial institutions for short-term financial returns to all investment, which reduces its capability to support innovative activities with a long lead-time. He contends that the solution to the UK's long-standing economic problems demands at least that technology and its proper management be placed at the very top of top management's agenda. He concludes the paper by challenging the technological community to play its part in bridging the gap between top managements and technology. Achieving acceptance of this challenge is the most important current task of those engaged in developing the management capabilities of scientists and technologists. The invitation to give an opening address, with no restrictions other than a loose relationship to the subject to be discussed, to a conference of this kind is one which is very difficult to refuse. Few of us can resist the chance of a platform on which to ride a few hobby-horses, display a few personal prejudices which can be legitimately exposed, and on which some wild generalisations can be made, which I would not make did I not think them worth further consideration. In this opening few minutes of your conference, I have no intention of examining any single aspect of the comprehensive coverage which will be the feature of the next three days, but I would like to deal personally with a few of the aspects of this most challenging of subjects of which I have had some personal experience. The subject is of crucial importance, not just in the operational sense of how we make the best of what we have, but in helping to formulate better the industrial strategies which the UK must adopt if it is to survive in the industrial jungle of the 21st century.

(1963). The Indian army in the Edinburgh military tattoo, 1962. Journal of The Royal Central Asian Society: Vol. 50, No. 1, pp. 47-49.