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.
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.
UK universities re-opened in September 2020, amidst the coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November; however, outbreaks among university students occurred. We aimed to measure the University of Bristol staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020–03/07/2020), relaxed guidance period (04/07/2020–13/09/2020), ‘rule-of-six’ period (14/09/2020–04/11/2020) and the second lockdown (05/11/2020–25/11/2020). In total, 722 staff (4199 responses) and 738 students (1906 responses) were included in the study. For staff, daily contacts were higher in the relaxed guidance and ‘rule-of-six’ periods than the post-first lockdown and second lockdown. Mean student contacts dropped between the ‘rule-of-six’ and second lockdown periods. For both staff and students, the proportion meeting with groups larger than six dropped between the ‘rule-of-six’ period and the second lockdown period, although was higher for students than for staff. Our results suggest university staff and students responded to national guidance by altering their social contacts. Most contacts during the second lockdown were household contacts. The response in staff and students was similar, suggesting that students can adhere to social distancing guidance while at university. The number of contacts recorded for both staff and students were much lower than those recorded by previous surveys in the UK conducted before the COVID-19 pandemic.
COVID-19 has had a significant impact on healthcare provision, accessibility and psychiatric presentations. We aim to investigate the impact of the pandemic on psychiatric services and the severity of presentations in Edinburgh, with a particular focus on the North-West Edinburgh Community Mental Health Team (NW CMHT).
Measures of the impact of the pandemic on NW CMHT were identified as referral numbers from primary care and Did Not Attend (DNA) rates. Royal Edinburgh Hospital admissions, detentions under the Mental Health (Care and Treatment) (Scotland) Act 2003 (MHA) and Out of Hours (OOH) contacts were used as proxy measures to explore the severity and urgency of presentations.
Quantitative data focussing on these parameters for patients aged 18–65 years in NW CMHT in 2019 and 2020 were collected from NHS Lothian Analytical Services. OOH data were only available Edinburgh-wide. All data were anonymised in line with NHS Lothian Information Governance Policy.
In order to assess the impact on staff, a questionnaire was created and disseminated, with qualitative data returned anonymously.
Referrals to NW CMHT decreased by 9.3% in 2020 (n = 2164) compared to 2019 (n = 2366). Referrals in April (n = 81) and May (n = 102) 2020 were far below the monthly average across the two years (n = 188).
Appointment numbers were very similar in 2019 (n = 3542) and 2020 (n = 3514). Despite this, DNA and cancellation rates decreased by 3.94% in 2020. Questionnaire results illustrated some of the challenges for staff of working during a pandemic.
Admissions to hospital reduced by 6.8% in 2020 (n = 219 vs n = 235). While MHA detentions in NW Edinburgh increased by only 1.8% (n = 173 vs n = 170), new Compulsory Treatment Orders (CTO) increased by 60%. Furthermore, OOH contacts across Edinburgh increased by 45.2% when compared to 2019.
The COVID-19 pandemic altered the way patients accessed healthcare. Uncertainty of the public in accessing primary care services early in the pandemic may have contributed to reduced referral numbers.
The increase in CTOs is suggestive of severe relapses in previously stable patients or new episodes of illness. The pandemic may have contributed to a reduction in early recognition, and referral, of those with major mental disorders resulting in more protracted or severe illness episodes. The increase in OOH crisis contacts supports such a hypothesis.
Despite what would be expected, DNA and cancellation rates in NW CMHT reduced. The contribution of telemedicine to this warrants further exploration as a means of delivering healthcare in an efficient and accessible way.
This quality improvement project aimed to assess the adherence of a hospital psychiatric liaison team's documentation of assessments to the Psychiatric Liaison Accreditation Network (PLAN) standards framework; to identify areas of improvement; to identify barriers to and improve adherence.
Data were extracted from 27 randomly selected patient assessments from 01/07/2020 to 31/08/2020 and then 27 assessments from 01/10/2020 to 30/11/2020 for re-audit.
Quantitative data was collected by calculating the percentage of assessments which documented each specific aspect of PLAN standards.
Qualitative data including attitudes specifically towards writing to patients was gathered from 1:1 discussions with members of staff.
Interventions between rounds of audit:
Presentation of results of 1st data collection to team in November 2020 followed by discussion
Emailed instructions to create a template based on PLAN standards for assessments to staff
Lobbied for Cerner access at liaison team office to facilitate use of above
Quantitative – overall improvements were seen in adherence to all aspects of documentation of assessments including collateral history (from 23% to 67%) past medical history (30% to 70%) and acknowledging the patient/carer perspective (46% to 74%). Some improvement was seen in offering written correspondence to patients (0% to 20%).
Qualitative – the majority of comments regarding writing to patients were positive, with no staff members opposing the standard (“it is best practice”, “should become a habit”). However, some barriers were identified including increased workload (“requires more editing”, “could take a lot more time”).
Team adherence to PLAN standards for documentation of assessments was improved through low intensity interventions. Overall adherence was high, however certain areas leave space for improvement. The audit facilitated conversations around writing to patients on discharge, both in the form of formal gathering of qualitative data and informal discussions between staff. Attitudes towards writing these letters were positive and some improvement was seen between audits. Ongoing audit activity aims to further improve adherence and monitor improvements.
To ensure that the PPE guidance is strictly adhered to.
To ensure that patient care is not compromised.
To help us in areas of need in order to educate the staff regarding the techniques of PPE and thus ensure patient and staff safety and care during the pandemic.
Novel coronavirus 2019 was first described in December 2019 in Wuhan in China. Since those initial few cases, it has rapidly proliferated to a global pandemic, putting an inordinate amount of strain on healthcare systems around the world. We believe that the technique of donning and doffing if followed as per PHE guidelines would be of help in both preventing the infection and improve the care and safety of both patients and staff.
This Audit includes both In-patient and Out-patient units in Psychiatric services across North Wales. Data were collected from 19 units out of 39. We observed covertly 325 staff members belonging to various cadres. Apart from the Donning and Doffing techniques, we also observed the availability of designated areas for this purpose and the availability of PPE as well.
Data collection was by junior and senior doctors from various sites of the mental health unit in North Wales. A proforma was provided, the standards were based on PHE guidelines.
It was noted that just about 50% of the staff followed donning as per guidance. Amongst all three sites, the Central team showed a better adherence with 85% of them donning PPE correctly. whereas only 22% adhered to donning in the West team.
Only 21% of them managed to doff PPE as per guidance amongst all 3 centres in North Wales.
It was also noted that there are no designated areas to Don and Doff in outpatient units. Staff, in general, seem to not adhere to the guidance of utilising a mask, especially when within 2 meters distance of other staff.
We will be presenting the Audit at the regional meeting. After discussion with the infection prevention control team and Health and safety lead, we intend to improvise the wards with designated areas for donning and doffing. Teaching sessions for the staff in all three sites, reminders in various areas of the community mental health units and inpatient units.
We are hoping that these recommendations will help us in achieving our aim of health and safety during this pandemic.
The Chronos 14Carbon-Cycle Facility is a new radiocarbon laboratory at the University of New South Wales, Australia. Built around an Ionplus 200 kV MIni-CArbon DAting System (MICADAS) Accelerator Mass Spectrometer (AMS) installed in October 2019, the facility was established to address major challenges in the Earth, Environmental and Archaeological sciences. Here we report an overview of the Chronos facility, the pretreatment methods currently employed (bones, carbonates, peat, pollen, charcoal, and wood) and results of radiocarbon and stable isotope measurements undertaken on a wide range of sample types. Measurements on international standards, known-age and blank samples demonstrate the facility is capable of measuring 14C samples from the Anthropocene back to nearly 50,000 years ago. Future work will focus on improving our understanding of the Earth system and managing resources in a future warmer world.
New material attributable to Deltasuchus motherali, a neosuchian from the Cenomanian of Texas, provides sampling across much of the ontogeny of this species. Detailed descriptions provide information about the paleobiology of this species, particularly with regards to how growth and development affected diet. Overall snout shape became progressively wider and more robust with age, suggesting that dietary shifts from juvenile to adult were not only a matter of size change, but of functional performance as well. These newly described elements provide additional characters upon which to base more robust phylogenetic analyses. The authors provide a revised diagnosis of this species, describing the new material and discussing incidents of apparent ontogenetic variation across the sampled population. The results of the ensuing phylogenetic analyses both situate Deltasuchus within an endemic clade of Appalachian crocodyliforms, separate and diagnosable from goniopholidids and pholidosaurs, herein referred to as Paluxysuchidae. This title is also available as Open Access on Cambridge Core.
Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
Social media summary
Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
When airway management is indicated, to avoid a bad outcome, patient safety will be maximised by careful decision making about and careful implementation of the chosen approach. This chapter addresses planning for the safest approach to securing the airway by assessing the patient for anatomical and physiological predictors of difficulty with airway management. When such difficulty is predicted, awake tracheal intubation will often provide the best margin of safety; indications for the procedure are discussed. Equally, when technical difficulty is predicted, the pre-conditions required to safely proceed with airway management after the induction of general anaesthesia are addressed. Predicted or not, difficulty encountered with tracheal intubation or supraglottic airway use in the unconscious patient must be met with a methodical and stepwise approach. This includes calling for help, maintaining patient oxygenation and methodically proceeding from one device type or technique to another, thus avoiding multiple futile attempts with the same device. Failure of a maximum of three attempts at the intended technique (most often tracheal intubation or use of a supraglottic airway) should be taken as an indication to refrain from further attempts, call for help, maintain patient oxygenation and reassess the plan for next steps. Finally, a ‘cannot intubate, cannot oxygenate’ situation is defined by the failure to successfully oxygenate the patient with all of tracheal intubation, face mask ventilation or a supraglottic airway and requires prompt front of neck airway access (‘surgical airway’).
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.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
Compared to the general population, individuals with complex congenital heart disease are at increased risk for deficits in cognitive, neurodevelopmental, psychosocial, and physical functioning, resulting in a diminished health-related quality of life. These deficits have been well described over the past 25 years, but significant gaps remain in our understanding of the best practices to improve neurodevelopmental and psychosocial outcomes and health-related quality of life for individuals with paediatric and congenital heart disease. Innovative clinical, quality improvement, and research opportunities with collaboration across multiple disciplines and institutions were needed to address these gaps. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with a described mission to determine and implement best practices of neurodevelopmental and psychosocial services for individuals and their families with paediatric and congenital heart disease through clinical, quality improvement, and research initiatives. The vision is to be a multi-centre, multi-national, multi-disciplinary group of healthcare professionals committed to working together and partnering with families to optimise neurodevelopmental outcomes for individuals with paediatric and congenital heart disease through clinical, quality, and research initiatives, intending to maximise quality of life for every individual across the lifespan. This manuscript describes the development and organisation of the Cardiac Neurodevelopmental Outcome Collaborative.
Health apps are software programs that are designed to prevent, diagnose, monitor, or manage conditions. Inconsistent terminology for apps is used in research literature and bibliographic database subject headings. It can therefore be challenging to retrieve evidence about them in literature searches. Information specialists at the United Kingdom's National Institute for Health and Care Excellence (NICE) have developed novel validated search filters to retrieve evidence about apps from MEDLINE and Embase (Ovid).
A selection of medical informatics journals was hand searched to identify a “gold standard” (GS) set of references about apps. The GS set was divided into a development and validation set. The filters’ search terms were derived from and tested against the development set. An external development set containing app references from published NICE products was also used to inform the development of the filters. The filters were then validated using the validation set. Target recall was >90 percent. The filters’ overall recall, specificity, and precision were calculated using all the references identified from the hand search.
Both filters achieved 98.6 percent recall against their validation sets. Overall, the MEDLINE filter had 98.8 percent recall, 71.3 percent specificity, and 22.6 percent precision. The Embase filter had 98.6 percent recall, 74.9 percent specificity, and 24.5 percent precision.
The NICE health apps search filters retrieve evidence about apps from MEDLINE and Embase with high recall. They can be applied to literature searches to retrieve evidence about the interventions by information professionals, researchers, and clinicians.
Background: Inappropriate ordering of urine cultures and the resulting unnecessary use of antibiotics can lead to complications of antimicrobial therapy including resistance, adverse effects (eg, disruption of microbiome and C. difficile infection), and increased healthcare costs, as well as the erroneous determination of CAUTI in patients with Foley catheters. A retrospective analysis of patients with CAUTI revealed frequent ordering of urine cultures for conditions and symptoms not supported by current IDSA guidelines. As a result, we created an action plan to reverse the trend of inappropriate urine culture ordering. Methods: Our urine culture reduction campaign was developed with input from the infectious disease service, antibiotic stewardship team (AST), infection prevention, pharmacy, and the microbiology service. The following educational efforts were included: (1) distribution of outpatient pocket cards with communication to providers about appropriate ordering of urine cultures; (2) creation of an evidence-based order set for urinalysis and urine cultures distributed electronically as emails and screensavers on computer stations and in person via didactic sessions with physicians and nursing staff; (3) a practice pointer for staff nurses that included recommended changes to urine culture ordering and encouraged open dialogue with physicians regarding the appropriateness of urine cultures; (4) didactic and personal communications to counter long-standing myths, such as “Urine cultures always for change in mental status”; (5) a peer-review process to evaluate and justify deviations from the testing algorithm.
Results: The first and second months after the introduction of the campaign, the microbiology laboratory reported 23% and 37% reductions in urine cultures ordered, respectively. During the same period, a 48% reduction in CAUTIs was reported for the entire health system. Conclusions: Reducing the number of inappropriate urine cultures is achievable with intense communication utilizing a multifaceted approach. With continued educational activities, we expect to sustain and even improve our successful reduction of inappropriate urine culture orders, ultimately improving patient outcomes.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.