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This paper presents a method used to rapidly assess the incursion and the establishment of community transmission of suspected SARS-CoV-2 variant of concern Delta (lineage B.1.617.2) into the UK in April and May 2021. The method described is independent of any genetically sequenced data, and so avoids the inherent lag times involved in sequencing of cases. We show that, between 1 April and 12 May 2021, there was a strong correlation between local authorities with high numbers of imported positive cases from India and high COVID-19 case rates, and that this relationship holds as we look at finer geographic detail. Further, we also show that Bolton was an outlier in the relationship, having the highest COVID-19 case rates despite relatively few importations. We use an artificial neural network trained on demographic data, to show that observed importations in Bolton were consistent with similar areas. Finally, using an SEIR transmission model, we show that imported positive cases were a contributing factor to persistent transmission in a number of local authorities, however they could not account for increased case rates observed in Bolton. As such, the outbreak of Delta variant in Bolton was likely not a result of direct importation from overseas, but rather secondary transmission from other regions within the UK.
Invasion and spread of alien species can drive ecosystem changes, such as, the dynamics of infectious diseases. The non-native, marine gastropod Crepidula fornicata has become established across European coastlines over the last century, but there remains little insight into its disease carrying capacity and potential role as a source/sink of parasites. To address this knowledge gap, we surveyed limpets from two sites in South Wales, UK for signatures of disease/pathology using polymerase chain reaction-based methods (haemolymph) and histology (solid tissue). We encountered trematode-like parasites in ~1% individuals (5 out of 462). Three limpets displayed gross damage in the gonad, i.e. castration, and encysted metacercariae were found in the muscle of two other individuals. On the basis of 28S rDNA and internal transcribed spacer 2 genomic targets, we identified the gonad-infecting trematodes as members of the family Microphallidae – putative novel species related to the genus Longiductotrema. Earlier reports suggest that C. fornicata is not a host for trematode parasites in either its native or alien range but may act as a sink due to its filter feeding lifestyle. We provide clear evidence that C. fornicata is parasitized by at least one trematode species at two sites in Wales, UK, and likely act as a spillback or accidental host among native littorinids.
Collective action is a pervasive aspect of political life in the 21st century. In the past 20 years, it has also been increasingly studied as a psychologically mediated and consequential form of political behaviour. Initial research focused primarily on the collective organisation of action. This was appropriate: collective action is inherently a group phenomenon. However, this chapter adapts the framework provided by Duncan (2012) to take a broader perspective to examine contemporary scholarship in relation to the individual, group, and contextual factors shaping collective action and its outcomes. We review literature emphasising a key role for individual differences in ideological beliefs and moral conviction, in shaping engagement in collective action. Life experiences such as contact with members of disadvantaged groups, and mobilising interactions (online and offline) have allowed people to co-act across ostensible category boundaries. The depth and breadth of the contemporary literature suggests the need for a broader meta-theory, drawing on the principles of dynamic interactionism, to allow us to more fully articulate what kinds of situations elicit mobilisation potential, and for whom.
Cardiac involvement associated with multi-system inflammatory syndrome in children has been extensively reported, but the prevalence of cardiac involvement in children with SARS-CoV-2 infection in the absence of inflammatory syndrome has not been well described. In this retrospective, single centre, cohort study, we describe the cardiac involvement found in this population and report on outcomes of patients with and without elevated cardiac biomarkers. Those with multi-system inflammatory syndrome in children, cardiomyopathy, or complex CHD were excluded. Inclusion criteriaz were met by 80 patients during the initial peak of the pandemic at our institution. High-sensitivity troponin T and/or N-terminal pro-brain type natriuretic peptide were measured in 27/80 (34%) patients and abnormalities were present in 5/27 (19%), all of whom had underlying comorbidities. Advanced respiratory support was required in all patients with elevated cardiac biomarkers. Electrocardiographic abnormalities were identified in 14/38 (37%) studies. Echocardiograms were performed on 7/80 patients, and none demonstrated left ventricular dysfunction. Larger studies to determine the true extent of cardiac involvement in children with COVID-19 would be useful to guide recommendations for standard workup and management.
To quantify the extent of food and beverage advertising on bus shelters in a deprived area of the UK, to identify the healthfulness of advertised products, and any differences by level of deprivation. The study also sought to assess the creative strategies used and extent of appeal to young people.
Design:
Images of bus shelter advertisements were collected via in person photography (in 2019) and Google Street View (photos recorded in 2018). Food and beverage advertisements were grouped into one of seventeen food categories and classified as healthy/less healthy using the UK Nutrient Profile Model. The deprivation level of the advertisement location was identified using the UK Index of Multiple Deprivation.
Setting:
Middlesbrough and Redcar and Cleveland in South Teesside.
Participants:
N/A
Results:
Eight hundred and thirty-two advertisements were identified, almost half (48·9 %) of which were for foods or beverages. Of food and non-alcoholic beverage adverts, 35·1 % were less healthy. Most food advertisements (98·9 %) used at least one of the persuasive creative strategies. Food advertisements were found to be of appeal to children under 18 years of age (71·9 %). No differences in healthiness of advertised foods were found by level of deprivation.
Conclusions:
Food advertising is extensive on bus shelters in parts of the UK, and a substantial proportion of this advertising is classified as less healthy and would not be permitted to be advertised around television programming for children. Bus shelter advertising should be considered part of the UK policy deliberations around restricting less healthy food marketing exposure.
This report examines between- and within-person associations between youth irritability and concurrent and prospective internalizing and externalizing symptoms from early childhood through adolescence. Distinguishing between- and within-person longitudinal associations may yield distinct, clinically relevant information about pathways to multifinality from childhood irritability.
Methods:
Children’s irritability and co-occurring symptoms were assessed across five waves between ages 3 and 15 years using the mother-reported Child Behavior Checklist (N = 605, 46% female). Parental history of depressive disorders was assessed with a clinical interview.
Results:
Results demonstrated that between- and within-person irritability were uniquely associated with concurrent depressive, anxiety, and defiance symptoms, but not ADHD. Prior wave within-person irritability also predicted next wave depressive, anxiety, and defiance symptoms, controlling for prior symptoms; these prospective associations were bidirectional. Child sex and parental depressive disorders moderated associations.
Discussions:
Findings identify pathways from within- and between-person irritability to later internalizing and externalizing psychopathology. Results demonstrate the importance of parsing within- and between-person effects to understand nuanced relations among symptoms over childhood.
The effectiveness of screening travellers during times of international disease outbreak is contentious, especially as the reduction in the risk of disease importation can be very small. Border screening typically consists of travellers being thermally scanned for signs of fever and/or completing a survey declaring any possible symptoms prior to admission to their destination country; while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we describe a simple Monte Carlo based model that incorporates the epidemiology of coronavirus disease-2019 (COVID-19) to investigate the potential decrease in risk of disease importation that might be achieved by requiring travellers to undergo screening upon arrival during the current pandemic. This is a purely theoretical study to investigate the maximum impact that might be attained by deploying a test or testing programme simply at the point of entry, through which we may assess such action in the real world as a method of decreasing the risk of importation. We, therefore, assume ideal conditions such as 100% compliance among travellers and the use of a ‘perfect’ test. In addition to COVID-19, we also apply the presented model to simulated outbreaks of influenza, severe acute respiratory syndrome (SARS) and Ebola for comparison. Our model only considers screening implemented at airports, being the predominant method of international travel. Primary results showed that in the best-case scenario, screening at the point of entry may detect a maximum of 8.8% of travellers infected with COVID-19, compared to 34.8.%, 9.7% and 3.0% for travellers infected with influenza, SARS and Ebola respectively. While results appear to indicate that screening is more effective at preventing disease ingress when the disease in question has a shorter average incubation period, our results suggest that screening at the point of entry alone does not represent a sufficient method to adequately protect a nation from the importation of COVID-19 cases.
The crystal structure of osimertinib mesylate Form B has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Osimertinib mesylate Form B crystallizes in space group P-1 (#2) with a = 11.42912(17), b = 11.72274(24), c = 13.32213(22) Å, α = 69.0265(5), β = 74.5914(4), γ = 66.4007(4)°, V = 1511.557(12) Å3, and Z = 2. The crystal structure is characterized by alternating layers of cation–anion and parallel stacking interactions parallel to the ab-planes. The cation is protonated at the nitrogen atom of the dimethylamino group, which forms a strong hydrogen bond between the cation and the anion. That hydrogen atom also participates in a weaker intramolecular hydrogen bond to an amino nitrogen. There are two additional N–H⋅⋅⋅O hydrogen bonds between the cation and the anion. Several C–H⋅⋅⋅O hydrogen bonds also link the cations and anions. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.
Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case–control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148⋅9 v. 131⋅7; P 0⋅01) and B6 lower (37⋅3 v. 52⋅9; P 0⋅01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.
Throughout the coronavirus disease 2019 (COVID-19) pandemic, health and social care workers have faced unprecedented professional demands, all of which are likely to have placed considerable strain on their psychological well-being.
Aims
To measure the national prevalence of mental health symptoms within healthcare staff, and identify individual and organisational predictors of well-being.
Method
The COVID-19 Staff Wellbeing Survey is a longitudinal online survey of psychological well-being among health and social care staff in Northern Ireland. The survey included four time points separated by 3-month intervals; time 1 (November 2020; n = 3834) and time 2 (February 2021; n = 2898) results are presented here. At time 2, 84% of respondents had received at least one dose of a COVID-19 vaccine. The survey included four validated psychological well-being questionnaires (depression, anxiety, post-traumatic stress and insomnia), as well as demographic and organisational measures.
Results
At time 1 and 2, a high proportion of staff reported moderate-to-severe symptoms of depression (30–36%), anxiety (26–27%), post-traumatic stress (30–32%) and insomnia (27–28%); overall, significance tests and effect size data suggested psychological well-being was generally stable between November 2020 and February 2021 for health and social care staff. Multiple linear regression models indicated that perceptions of less effective communication within their organisation predicted greater levels of anxiety, depression, post-traumatic stress and insomnia.
Conclusions
This study highlights the need to offer psychological support to all health and social care staff, and to communicate with staff regularly, frequently and clearly regarding COVID-19 to help protect staff psychological well-being.
Psychiatric hospitals are well equipped to manage patients with complex psychiatric needs, however due to their community setting when a rare medical emergency occurs it is not unusual for a small delay whilst staff search for equipment on the ward or even go to other wards for equipment. The aim of this audit is to ensure that our psychiatric wards in Carseview Centre are well equipped to respond to patients becoming medically unwell and put our nurses and doctors in a position to safely stabilise the patient until furthur help arrives.
Method
We collected data from 3 inpatient adult wards, 1 intensive psychiatric care unit and 1 learning disability unit and compared their resuscitation trolley equipment with local NHS Tayside Emergency Equipment Protocol in January 2020. Following data collection we fed back to the wards about our results and discussions were held between doctors, charge nurses, pharmacists and resuscitation officers to determine whether missing equipment were neccesary in the community setting and to see if there were updates that required for our local protocol to better reflect current practices as it had not been reviewed since 2012. Following multiple meetings we amended our local protocol to better reflect what was . A list of recommendations was also made to improve patient safety.
We then collected data again in January 2021
Result
Folloing our first data collection we found that the resuscitation trolleys tended to not have ligature packs and masks were generally not by the oxygen cylinders. Hypoglycaemic dextro-tablets were also not readily available. The Learning disability units also did not have an emergency resuscitation trolley.
Following our discussions and amendment of the protocol this was finalised in November 2020 and was dissemindated towards the wards and we waited 2 months for the changes to take effects and recollected our data. There continued to be equipment that was incomplete/missing on each individual ward, but none that were consistent throughout the whole hospital site. All the recommendations that were made for the 1st data collection had been done.
Conclusion
Overall we felt that the emergency trolleys were better equipped in line with the updated protocol compared to the previous audit cycle. The overall pattern of missing equipment was inconsistent and the recommendation was for staff to copmlete checks to address missing/incomplete items when found. Our local protocol also recommends that all ward should stock ‘additional items’ (nebuliser masks and non-rebreather masks), which majority had however were difficult to locate, which could delay patient care.
We will continue to repeat data collection cycles and feedback to our wards to ensure patient safety is not compromised.
Kinetoplastid parasites are responsible for both human and animal diseases across the globe where they have a great impact on health and economic well-being. Many species and life cycle stages are difficult to study due to limitations in isolation and culture, as well as to their existence as heterogeneous populations in hosts and vectors. Single-cell transcriptomics (scRNA-seq) has the capacity to overcome many of these difficulties, and can be leveraged to disentangle heterogeneous populations, highlight genes crucial for propagation through the life cycle, and enable detailed analysis of host–parasite interactions. Here, we provide a review of studies that have applied scRNA-seq to protozoan parasites so far. In addition, we provide an overview of sample preparation and technology choice considerations when planning scRNA-seq experiments, as well as challenges faced when analysing the large amounts of data generated. Finally, we highlight areas of kinetoplastid research that could benefit from scRNA-seq technologies.
We review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic–pituitary–adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic–racial disparities in stress biology and in emotional health and academic outcomes.
This chapter tells the story of a research-engagement project called Making, Mapping and Mobilising in Merthyr (otherwise known as the 4Ms project). The project explored young people's sense of place and well-being while growing up in Merthyr Tydfil (hereafter referred to as Merthyr), a small post-industrial ex-mining and steel-making town of roughly 58,000 people in the South Wales Valleys. Once a hub of industrial activity and innovation, along with other geographically close regions, Merthyr has experienced a deep social rupture in recent years owing to deindustrialisation and the closure of ironworks, coal mines and manufacturing industries that had served as cultural links underpinning the rhythms and rituals of Valleys life (Walkerdine and Jimenez, 2011; Ivinson, 2014). Our project took place predominantly in a housing estate based on a design reputed to have been inspired in the 1950s by romantic Italian hilltop villages. The estate expanded in the 1970s, and by the 2000s, had become dilapidated and a place with high levels of unemployment. In a context of tightening austerity, this housing estate and the people living there have been subject to stigmatising media accounts fuelled by television's ‘poverty porn’ industry (Tyler, 2015) and, at times, by local residents themselves (Byrne et al, 2016; Thomas, 2016). The ‘realities’ of poverty tend to be portrayed in popular media through no-hope narratives of despair (Thomas, 2016; Thomas et al, 2018).
In contrast to other projects in the Productive Margins programme, the 4Ms project did not set out to investigate a specific element of regulation. Rather, we approached regulation as it occurred through the everyday experiences of living in a place that is in many ways at the margins, in terms of the explicit as well as the hidden effects and affects of poverty. The initial aim of the project was thus to attune to young people's knowledge as experts of living in this post-industrial place and to co-create research methods and encounters in order to find out how a range of regulatory regimes mediate and impact on their everyday lives.
The 4Ms project took shape across a series of three overlapping phases. We began by exploring the affective contours of the young people's neighbourhoods (Thomas, 2016).
Managed access arrangements (MAAs) represent a way of enabling patient access to promising treatments while collecting real world data to inform future health technology evaluations (HTE) and commissioning decisions. In July 2016, the National Institute for Health and Care Excellence (NICE) recommended Ataluren for treating Duchenne Muscular Dystrophy within a MAA. NICE is uniquely placed to oversee the implementation and monitoring of this MAA in collaboration with multiple stakeholders to ensure the final outputs meet the needs of a future HTE.
Methods
NICE assembled an Ataluren Managed Access Oversight Committee (MAOC) consisting of representatives from the manufacturer, patient organisations, commissioning body and treatment centres. This group were to meet every six months under the chairmanship of NICE with the primary function of reviewing the progress of data collection and identifying operational challenges in implementing the terms of the arrangement.
Results
The Ataluren MAOC has convened four times since the MAA commenced and these discussions identified a number of important actions. Data completeness was a concern and prompted stakeholders to collaborate on implementing measures to circumvent this, to ensure data quality for future HTE. Lack of awareness and understanding of the MAA in the patient community was highlighted and resulted in the production of lay information. A review of the statistical analysis plan resulted in the need for an agreement amendment. To ensure an audit trail and appropriate critique, NICE produced an amendment process to define and justify amendments made during the agreement term.
Conclusions
MAOC meetings play an important role in monitoring the progress of MAAs and have ensured that implementation issues are identified promptly and resolved with input from key stakeholders. This process allows NICE to coordinate the work of stakeholders to facilitate the success of the MAA, and will be adopted in future NICE MAAs in ultra-rare diseases.
The need for the adoption of a capacity mechanism in France has primarily been justified by reasons of security of electricity supply. Following a market-based and country-wide approach, the French authorities have made the choice of a Capacity Market as the main capacity remuneration mechanism. The rules for the Capacity Market have been progressively developed since 2010 until the adoption of a detailed regime in 2015. Despite delays related to legal proceedings and the need to rapidly adjust the capacity mechanism design in order to secure State aid approval, the first capacity auction took place in December 2016. This chapter analyses the Capacity Market introduced in France by examining: the evolution of its legislative and regulatory framework and related litigation; its current regime; the modifications induced by the European Commission's decisions on State aid control; and finally an overview of the market practices and some perspectives.
BACKGROUND FOR THE INTRODUCTION OF A CAPACITY MECHANISM IN FRANCE
SECURITY OF SUPPLY AS A PRIMARY CONCERN
The security of the supply of electricity to consumers, which can be defined as: ‘the ability of energy systems to satisfy continuously and at a reasonable cost, the expected market demand’, has been the focus of the French energy transition.
The latter has recently been reaffirmed as part of the ‘Multiannual Energy Programme’ (programmation pluriannuelle de l’énergie, PPE) of 2016 which sets out the Government's energy policy for the next five years, in accordance with the objectives defined in the 2015 Energy Transition Law for Green Growth. The PPE is subject to a revision process in 2018.
Security of supply is a complex issue as a constant balance must be maintained in the network between the production and the consumption of electricity. Additional complicating factors are related to the fact that, on the one hand, electricity cannot be stored in sufficient quantities, and, on the other hand, electricity consumption is variable depending on the time of day and the season.
In France, the main challenge facing security of supply is caused by the winter consumption peak due to consumption that is ‘highly heat sensitive’, given the predominance of electric heating.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Whitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.
There is now a clear focus on incorporating, and integrating, multiple levels of analysis in developmental science. The current study adds to research in this area by including markers of the immune and neuroendocrine systems in a longitudinal study of temperament in infants. Observational and parent-reported ratings of infant temperament, serum markers of the innate immune system, and cortisol reactivity from repeated salivary collections were examined in a sample of 123 infants who were assessed at 6 months and again when they were, on average, 17 months old. Blood from venipuncture was collected for analyses of nine select innate immune cytokines; salivary cortisol collected prior to and 15 min and 30 min following a physical exam including blood draw was used as an index of neuroendocrine functioning. Analyses indicated fairly minimal significant associations between biological markers and temperament at 6 months. However, by 17 months of age, we found reliable and nonoverlapping associations between observed fearful temperament and biological markers of the immune and neuroendocrine systems. The findings provide some of the earliest evidence of robust biological correlates of fear behavior with the immune system, and identify possible immune and neuroendocrine mechanisms for understanding the origins of behavioral development.
Background: Speech pathologists work to optimise communication and reduce the emotional and social impact of communication disability in patients with aphasia but need evidence-based interventions to effectively do so.
Objective: This phase 1 study aims to evaluate an Australian speech-pathology-led intervention called the Aphasia Action, Success, and Knowledge (Aphasia ASK) programme for patients with aphasia early post stroke.
Methods: A convergent parallel mixed-methods design was utilised. The intervention included up to six individual face-to-face sessions with seven participants with aphasia and their nominated family member(s). Quantitative outcomes assessing mood, quality of life, and communication confidence were conducted for the participants with aphasia. Follow-up interviews were conducted with both participants with aphasia and family members to determine their perceptions of the programme.
Results: Significant improvements were found in communication confidence and mood after treatment and the gains were maintained at 3-month follow-up. Participants with aphasia and their family members reported a good level of satisfaction with the programme.
Conclusions: Findings suggest the Aphasia ASK programme is a suitable intervention with positive initial outcomes for people with aphasia. A larger scale evaluation with a greater variety of participants is now required. An Australian cluster randomised control trial is planned.