To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This edited collection of essays brings together leading scholars of early modern drama and playhouse culture to reflect upon the study of playing and playgoing in early modern England. With a particular focus on the player-playgoer exchange as a site of dramatic meaning-making, this book offers a timely and significant critical intervention in the field of Shakespeare and early modern drama. Working with and reflecting upon approaches drawn from literary scholarship, theatre history and performance studies, it seeks to advance the critical conversation on the interactions between: players; play-texts; performance spaces; the bodily, sensory and material experiences of the playhouse; and playgoers' responses to, and engagements with, the theatre. Through alternative methodological and theoretical approaches, previously unknown or overlooked evidence, and fresh questions asked of long-familiar materials, the volume offers a new account of early modern drama and performance that seeks to set the agenda for future research and scholarship.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Background: Accurately tracing nosocomial transmission of coronavirus disease 2019 (COVID-19) is critical to developing effective infection prevention policies. Given the high prevalence and variable incubation period of SARS-CoV-2 infection, the utility of traditional contact tracing is limited. We describe a nosocomial outbreak in which whole-genome sequencing (WGS) was pivotal to identifying the primary case. Methods: This study was conducted at a New York City academic hospital. The index case was identified on August 13, 2020, and the last case on September 9, 2020. Hospital policy required all inpatients to be screened for COVID-19 on admission by SARS-CoV-2 molecular amplification testing. All healthcare workers (HCWs) were required to wear masks and eye protection for patient care. After a patient (patient 1), who tested SARS-CoV-2 negative on admission, was positive on preprocedure screening on hospital day 9, contact tracing was initiated. Two patients (patients 2 and 3) and 13 HCWs with high-risk exposures (HREs) to patient 1 were quarantined and referred for testing. Additional surveillance testing was performed on 18 inpatients and 84 HCWs on the affected unit. Patients 2 and 3 and 3 HCWs (HCW-1, -2, and -3), only 1 of whom had a high-risk exposure to patient 1, tested positive. WGS was performed to further investigate this outbreak. Results: The outbreak variant (clade 20A) was found in samples from 6 patients and 2 HCWs. Patients 2 and 3 were roommates of patient 1 in the 2 days before patient 1’s positive test, and they did not consistently wear masks in the room. HCW-1 placed a peripheral IV in patient 1 the day before patient 1’s positive test without wearing eye protection. Four additional cases in this cluster (patients 4–6 and HCW-4) were identified by surveillance WGS of positive tests. A review indicated that patient 1 was located ~3 m (~10 feet) away from patient 4 in the emergency department (ED) for 6 hours on hospital day 1, when the admission SARS-CoV-2 test from patient 4 was not positive. No epidemiologic link was found to patient 5 or 6 or HCW-4. The specimen from HCW-2 was inadequate for WGS. The specimen from HCW-3 was not linked to this cluster. Conclusions: This complex nosocomial outbreak highlights the importance of WGS in understanding transmission events. Patient 4 was not identified by traditional contact tracing but was linked to patient 1 and was recognized as the primary case through WGS, having likely infected patient 1 in the ED. Based on these findings, we focused our corrective actions on more promptly isolating suspected COVID-19 cases in the ED, increasing inpatient masking, and improving HCW adherence to universal eye protection.
A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose–response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for ‘real-world’ cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D’s importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.
The Bronze Age in Britain is now a term often used to include both the first use of copper c. 2400 bc and also tin-bronze from c. 2100 bc, all of which required the extensive use of copper. Prehistoric mining for this metal has been identified in surface and underground workings in Parys Mine, Mynydd Parys, Anglesey, although almost all of the surface workings are now obscured by the extensive deep spoil from more recent mining in the industrial period. These copper-bearing ores are in bedded lodes, together with some intruded vein deposits. The Bronze Age workings have been exposed underground where they have been intersected by the early 19th century industrial workings on and above the 16 fathom and 20 fathom levels in the Parys Mine. Spoil exposures contain stone hammers (‘mauls’), wood fragments, and charcoal; samples of the latter have been radiocarbon dated with chronological modelling suggesting activity took place in the first half of the 2nd millennium cal bc. Although relatively limited in extent, these important prehistoric mining sites are among the earliest found in the UK. They have survived due to their protection from surface erosion and limited accessibility.
This paper reports on a study which examined the notions of authenticity and citizenship for people living with cognitive impairment or dementia in a care home in the North-East of England. We demonstrated that both notions were present and were encouraged by engagement with an artist, where this involved audio and visual recordings and the creation of a film. The artist's interactions were observed by a non-participant observer using ethnographic techniques, including interviews with the residents, their families and the staff of the care home. The data were analysed using grounded theory and the constant comparative method of qualitative analysis. Our findings suggest that participatory art might help to maintain and encourage authenticity and citizenship in people living with dementia in a care home. Certainly, authenticity and citizenship are notions worth pursuing in the context of dementia generally, but especially in care homes.
To describe the neuroimaging and other methods for assessing vascular contributions to neurodegeneration in the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study, a Canadian multi-center, prospective longitudinal cohort study, including reliability and feasibility in the first 200 participants.
COMPASS-ND includes persons with Alzheimer’s disease (AD; n = 150), Parkinson’s disease (PD) and Lewy body dementias (LBDs) (200), mixed dementia (200), mild cognitive impairment (MCI; 400), subcortical ischemic vascular MCI (V-MCI; 200), subjective cognitive impairment (SCI; 300), and cognitively intact elderly controls (660). Magnetic resonance imaging (MRI) was acquired according to the validated Canadian Dementia Imaging Protocol and visually reviewed by either of two experienced readers blinded to clinical characteristics. Other relevant assessments include history of vascular disease and risk factors, blood pressure, height and weight, cholesterol, glucose, and hemoglobin A1c.
Analyzable data were obtained in 197/200 of whom 18 of whom were clinically diagnosed with V-MCI or mixed dementia. The overall prevalence of infarcts was 24.9%, microbleeds was 24.6%, and high white matter hyperintensity (WMH) was 31.0%. MRI evidence of a potential vascular contribution to neurodegeneration was seen in 12.9%–40.0% of participants clinically diagnosed with another condition such as AD. Inter-rater reliability was good to excellent.
COMPASS-ND will be a useful platform to study vascular brain injury and its association with risk factors, biomarkers, and cognitive and functional decline across multiple age-related neurodegenerative diseases. Initial findings show that MRI-defined vascular brain injury is common in all cognitive syndromes and is under-recognized clinically.
The COVID-19 global pandemic has had considerable health impact, including sub-Saharan Africa. In Malawi, a resource-limited setting in Africa, gaining access to data to inform the COVID-19 response is challenging. Information on adherence to physical distancing guidelines and reducing contacts are nonexistent, but critical to understanding and communicating risk, as well as allocating scarce resources. We present a case study which leverages aggregated call detail records into a daily data pipeline which summarize population density and mobility in an easy-to-use dashboard for public health officials and emergency operations. From March to April 2021, we have aggregated 6-billion calls and text messages and continue to process 12 million more daily. These data are summarized into reports which describe, quantify, and locate mass gatherings and travel between subdistricts. These reports are accessible via web dashboards for policymakers within the Ministry of Health and Emergency Operations Center to inform COVID-19 response efforts and resource allocation.
The 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.
The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.
To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.
Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.
Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.
These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.
Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination.
To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators.
We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews.
Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized.
In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale.
Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
Children with autism spectrum disorder (ASD) have increased susceptibility to anxiety disorders. Variation in a common ASD symptom, insistence on sameness behaviour, may predict future anxiety symptoms.
To describe the joint heterogeneous longitudinal trajectories of insistence on sameness and anxiety in children with ASD and to characterise subgroups at higher risk for anxiety.
In a longitudinal ASD cohort (n = 421), insistence on sameness behaviour was measured using the Autism Diagnostic Interview-Revised at approximately ages 3, 6 and 11 years. Anxiety was quantified at 8 time points between ages 3 and 11 years using the Child Behavior Checklist (CBCL) (parent report). Clusters of participants following similar trajectories were identified using group-based and joint trajectory modelling.
Three insistence on sameness trajectories were identified: (a) ‘low-stable’ (41.7% of participants), (b) ‘moderate-increasing’ (52.0%) and (c) ‘high-peaking’ (i.e. increasing then stabilising/decreasing behaviour) (6.3%). Four anxiety trajectories were identified: (a) ‘low-increasing’ (51.0%), (b) ‘moderate-decreasing’ (16.2%), (c) ‘moderate-increasing’ (19.6%) and (d) ‘high-stable’ (13.1%). Of those assigned to the ‘high-peaking’ insistence on sameness trajectory, 95% jointly followed an anxiety trajectory that surpassed the threshold for clinical concern (T-score >65) by middle childhood (anxiety trajectories 3 or 4). Insistence on sameness and anxiety trajectories were similar in severity and direction for 64% of the sample; for 36%, incongruous patterns were seen (e.g. decreasing anxiety and increasing insistence on sameness).
The concurrent assessment of insistence on sameness behaviour and anxiety in ASD may help in understanding current symptom profiles and anticipating future trajectories. High preschool insistence on sameness in particular may be associated with elevated current or future anxiety symptoms.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
In recent years the plethora of ‘weird wonders,’ the vernacular for the apparently extinct major body plans documented in many of the Cambrian Lagerstätten, has been dramatically trimmed. This is because various taxa have been either assigned to known phyla or accommodated in larger monophyletic assemblages. Nevertheless, a number of Cambrian taxa retain their enigmatic status. To this intriguing roster we add Dakorhachis thambus n. gen. n. sp. from the Miaolingian (Guzhangian) Weeks Formation Konservat-Lagerstätte of Utah. Specimens consist of an elongate body that lacks appendages but is apparently segmented. A prominent feeding apparatus consists of a circlet of triangular teeth, while posteriorly there are three distinct skeletal components. D. thambus is interpreted as an ambush predator and may have been partially infaunal. The wider affinities of this new taxon remain conjectural, but it is suggested that it may represent a stem-group member of the Gnathifera, today represented by the gnathostomulids, micrognathozoans, and rotifers and possibly with links to the chaetognaths.
Cancer is the second leading cause of death worldwide. Lifestyle choices play an important role in the aetiology of cancer with up to 4 in 10 cases potentially preventable. Interventions delivered by healthcare professionals (HCPs) that incorporate risk information have the potential to promote behaviour change. Our aim was to develop a very brief intervention incorporating cancer risk, which could be implemented within primary care.
Guided by normalisation process theory (NPT), we developed a prototype intervention using literature reviews, consultation with patient and public representatives and pilot work with patients and HCPs. We conducted focus groups and interviews with 65 HCPs involved in delivering prevention activities. Findings were used to refine the intervention before 22 HCPs completed an online usability test and provided further feedback via a questionnaire incorporating a modified version of the NoMAD checklist.
The intervention included a website where individuals could provide information on lifestyle risk factors view their estimated 10-year risk of developing one or more of the five most common preventable cancers and access lifestyle advice incorporating behaviour change techniques. Changes incorporated from feedback from the focus groups and interviews included signposting to local services and websites, simplified wording and labelling of risk information. In the usability testing, all participants felt it would be easy to collect the risk information. Ninety-one percent felt the intervention would enable discussion about cancer risk and believed it had potential to be easily integrated into National Health Service (NHS) Health Checks. However, only 36% agreed it could be delivered within 5 min.
With the use of NPT, we developed a very brief intervention that is acceptable to HCPs in primary care and could be potentially integrated into NHS Health Checks. However, further work is needed to assess its feasibility and potential effectiveness.