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Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
The IntCal family of radiocarbon (14C) calibration curves is based on research spanning more than three decades. The IntCal group have collated the 14C and calendar age data (mostly derived from primary publications with other types of data and meta-data) and, since 2010, made them available for other sorts of analysis through an open-access database. This has ensured transparency in terms of the data used in the construction of the ratified calibration curves. As the IntCal database expands, work is underway to facilitate best practice for new data submissions, make more of the associated metadata available in a structured form, and help those wishing to process the data with programming languages such as R, Python, and MATLAB. The data and metadata are complex because of the range of different types of archives. A restructured interface, based on the “IntChron” open-access data model, includes tools which allow the data to be plotted and compared without the need for export. The intention is to include complementary information which can be used alongside the main 14C series to provide new insights into the global carbon cycle, as well as facilitating access to the data for other research applications. Overall, this work aims to streamline the generation of new calibration curves.
Understanding parents’ communication preferences and how parental and child characteristics impact satisfaction with communication is vital to mitigate communication challenges in the cardiac ICU.
This cross-sectional survey was conducted from January 2019 to March 2020 in a paediatric cardiac ICU with parents of patients admitted for at least two weeks. Family satisfaction with communication with the medical team was measured using the Communication Assessment Tool for Team settings. Clinical characteristics were collected via Epic, Pediatric Cardiac Critical Care Consortium local entry and Society for Thoracic Surgeons Congenital Heart Surgery Databases. Associations between communication score and parental mood, stress, perceptions of clinical care, and demographic characteristics along with patient demographic and clinical characteristics were examined. Multivariable ordinal models were conducted with characteristics significant in bivariate analysis.
In total, 93 parents of 84 patients (86% of approached) completed surveys. Parents were 63% female and 70% White. Seventy per cent of patients were <6 months old at admission, 25% had an extracardiac abnormality, and 80% had a cardiac surgery this admission. Parents of children with higher pre-surgical risk of mortality scores (OR 2.875; 95%CI 1.076–7.678), presence of surgical complications (72 [63.0, 75.0] vs. 64 [95%CI 54.6, 73] (p = 0.0247)), and greater satisfaction with care in the ICU (r = 0.93922; p < 0.0001) had significantly higher communication scores.
These findings can prepare providers for scenarios with higher risk for communication challenges and demonstrate the need for further investigation into interventions that reduce parental anxiety and improve communication for patients with unexpected clinical trajectories
Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.
This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.
A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.
The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
OBJECTIVES/GOALS: The purpose of this small survey-based study was to characterize the current role of neurocritical care physicians in traumatic brain injury (TBI) systems of care and research. In doing so, we aim to highlight potential roles of neurology providers in the medical management and enhancement of translational science in the field of TBI. METHODS/STUDY POPULATION: Between April and June 2021, a web-based survey was disseminated by email to members of the Neurocritical Care Society. The survey was open to all physician providers. A total of 36 surveys were completed. The survey consisted of 18 questions with pre-defined answer choices. Survey questions aimed to determine areas of practice, primary clinical specialty, hospital practice setting, provider involvement in TBI care, provider involvement in TBI research, and current research roles. RESULTS/ANTICIPATED RESULTS: 92% of survey respondents were in the United States (n=33), representing all national regions. 75% of the physicians were neurocritical care trained (n=27). 69% of providers were practicing in academic institutions while 78% were at sites designated as Level I trauma centers. All respondents managed acute TBI, but 50% served as consultants rather than being the primary service provider. At their sites of practice, 31% of patients were on non-neuroscience services, especially those with non-neurologic traumatic injury. Only 36% reported that TBI protocols were written and adhered to at their site. Only 44% reported that TBI research was performed at their site, while 50% had interest in participating in TBI research. TBI was the primary area of research for 17% of physicians. DISCUSSION/SIGNIFICANCE: This small physician survey highlights heterogeneity in TBI systems-based practice and research roles. Areas of potential improvement include greater involvement of neurocritical care physicians in TBI management, protocol-building and implementation, and TBI research. Reasons for current barriers are multifactorial and will be discussed.
Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012–2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46–59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.
Tree-ring series offer considerable potential for the development of environment-sensitive proxy records. However, with traditional increment cores, only small amounts of wood are often available from annual tree-ring sequences. For this reason, it is important to understand the reliability (and reproducibility) of radiocarbon measurements obtained from small-sized samples. Here we report the F14C results from the Chronos 14Carbon-Cycle Facility of modern tropical Australian tree samples over a range of four graphite target sizes from the same rings. Our study shows that similar precision can be obtained from full-sized, half-sized, as well as small-sized graphite targets using standard pretreatment and analysis procedures. However, with a decline in sample size, there was an increase seen in the associated variance of the ages and the smallest target weights started showing a systematic bias. Wiggle-matching accuracy tests, comparing the Southern Hemisphere post-bomb atmospheric calibration curve to the different sample weight sequences, were all significant except for the 200 μgC graphite targets. Our results indicate that samples smaller than 350 μgC have limited accuracy and precision. Overall, reliable measurements of F14C sequences from tree-ring records across a range of sample sizes, with best results found using graphitized samples >350 μgC.
While quantum accelerometers sense with extremely low drift and low bias, their practical sensing capabilities face at least two limitations compared with classical accelerometers: a lower sample rate due to cold atom interrogation time; and a reduced dynamic range due to signal phase wrapping. In this paper, we propose a maximum likelihood probabilistic data fusion method, under which the actual phase of the quantum accelerometer can be unwrapped by fusing it with the output of a classical accelerometer on the platform. Consequently, the recovered measurement from the quantum accelerometer is used to estimate bias and drift of the classical accelerometer which is then removed from the system output. We demonstrate the enhanced error performance achieved by the proposed fusion method using a simulated 1D accelerometer precision test scenario. We conclude with a discussion on fusion error and potential solutions.
Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43–8.03), social care (aOR 2.63, 1.22–5.67) or healthcare (aOR 2.31, 1.29–4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03–4.62), visit a pub (aOR 2.87, 1.11–7.37) and smoke or vape (aOR 1.54, 1.02–2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.
Sleep is vital for health and wellbeing across the lifecourse. Ethnic differences have been observed with regards to the prevalence and predictors of self-reported sleep problems. An understanding of sleep experiences with ageing and across ethnicities is required to better support older people. Open-ended interviews were conducted with 23 people living in Aotearoa/New Zealand aged 61–92 years (12 Māori and 11 non-Māori) concerning current sleep status, changes over their lifecourse and personal strategies for supporting good sleep. Participants typically expressed satisfaction with current sleep (usually pertaining to duration) or feelings that sleep was compromised (usually pertaining to waking function). Comparisons to a socially perceived ‘ideal’ sleep were common, with sleep transitions presented as a gradual and accepted part of ageing. Participants resisted medicalising sleep disruptions in older age. While participants were aware of ways to enhance their sleep, many acknowledged engaging in practices that undermined it. Unique insights from some Māori participants indicated that sleep disruptions were not so readily pathologised compared to Western views and that sleeplessness could provide opportunity for cultural or spiritual connection. Common narratives underpinning the themes were: ‘You don't need as much sleep when you're older’, ‘Sleep just fits in’ and ‘Having the time of my life’. Findings provide personal experiences and cultural interpretations relating to sleep and ageing. This provides the foundation for future participatory research to co-design sleep health messages which are meaningful for ageing well across ethnicities.
In recent decades, the use of conditionality backed by benefit sanctions for those claiming unemployment and related benefits has become widespread in the social security systems of high-income countries. Critics argue that sanctions may be ineffective in bringing people back to employment or indeed harmful in a range of ways. Existing reviews largely assess the labour market impacts of sanctions but our understanding of the wider impacts is more limited. We report results from a scoping review of the international quantitative research evidence on both labour market and wider impacts of benefit sanctions. Following systematic search and screening, we extract data for 94 studies reporting on 253 outcome measures. We provide a narrative summary, paying attention to the ability of the studies to support causal inference. Despite variation in the evidence base and study designs, we found that labour market studies, covering two thirds of our sample, consistently reported positive impacts for employment but negative impacts for job quality and stability in the longer term, along with increased transitions to non-employment or economic inactivity. Although largely relying on non-experimental designs, wider-outcome studies reported significant associations with increased material hardship and health problems. There was also some evidence that sanctions were associated with increased child maltreatment and poorer child well-being. Lastly, the review highlights the generally poor quality of the evidence base in this area, with few studies employing research methods designed to identify the causal impact of sanctions, especially in relation to wider impacts.
In the UK, postnatal depression is more common in British South Asian women than White Caucasion women. Cognitive–behavioural therapy (CBT) is recommended as a first-line treatment, but there is little evidence for the adaptation of CBT for postnatal depression to ensure its applicability to different ethnic groups.
To evaluate the clinical and cost-effectiveness of a CBT-based positive health programme group intervention in British South Asian women with postnatal depression.
We have designed a multicentre, two-arm, partially nested, randomised controlled trial with 4- and 12-month follow-up, comparing a 12-session group CBT-based intervention (positive health programme) plus treatment as usual with treatment as usual alone, for British South Asian women with postnatal depression. Participants will be recruited from primary care and appropriate community venues in areas of high South Asian density across the UK. It has been estimated that randomising 720 participants (360 into each group) will be sufficient to detect a clinically important difference between a 55% recovery rate in the intervention group and a 40% recovery rate in the treatment-as-usual group. An economic analysis will estimate the cost-effectiveness of the positive health programme. A qualitative process evaluation will explore barriers and enablers to study participation and examine the acceptability and impact of the programme from the perspective of British South Asian women and other key stakeholders.
Conservation lacks sufficient well-trained leaders who are empowered to catalyse positive change for the natural world. Addressing this need, the University of Cambridge launched a Masters in Conservation Leadership in 2010. The degree includes several features designed to enhance its impact. Firstly, it recruits international, gender-balanced cohorts of mid-career professionals, building leadership capacity in the Global South and providing a rich environment for peer learning. Secondly, teaching includes applied leadership training in topics such as fundraising, leading people and networking, as well as interdisciplinary academic topics. Thirdly, the degree is delivered through the Cambridge Conservation Initiative, a partnership of international NGOs and networks, facilitating extensive practitioner-led and experiential learning. We present details of programme design and evaluate the impact of the Masters after 10 years, using data from course records, student and alumni perspectives, and interviews with key stakeholders. The course has broadly succeeded in its design and recruitment objectives. Self-assessed leadership capabilities, career responsibilities and the overall impact of alumni increased significantly 5 years after graduation. However, specific impacts of alumni in certain areas, such as on their professional colleagues, have been less clear. We conclude by outlining future plans for the Masters in light of growing demands on conservation leaders and the changing landscape of leadership capacity development. These include reforms to course structure and assessment, long-term support to the alumni network and developing a conservation leadership community of practice.
The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.
Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.
Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = −0.41), peritraumatic distress (d = −0.24), and experiential avoidance (d = −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = −0.94), depression (d = −0.23), anxiety (d = −0.29), and experiential avoidance (d = −0.30).
Significance of results
Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.
Psychiatric prescribers typically assess adherence by patient or caregiver self-report. A new digital medicine (DM) technology provides objective data on adherence by using an ingestible event monitoring (IEM) sensor embedded within oral medication to track ingestion. Despite likely clinical benefit, adoption by prescribers will in part depend on attitudes toward and experience with digital health technology, learning style preference (LSP), and how the technology s utility and value are described.
is to identify attitudes, experiences, and proclivities toward DM platforms that may affect adoption of the IEM platform and provide direction on tailoring educational materials to maximize adoption. Methods A survey of prescribers treating seriously mentally ill patients was conducted to assess drivers/barriers to IEM adoption. Factor analysis was performed on 13 items representing prior experience with and attitudes toward DM. Factor scores were correlated with prescriber characteristics including attitude and experience with digital technologies, LSP, and level of focus on healthcare cost.
A total of 127 prescribers (56% female, 76% physicians, mean age 48.1yrs.) completed the survey. Over 90% agreed medication adherence is important, visits allow enough time to monitor adherence (84.1%), and tailoring treatment to level of adherence would be beneficial (92.9%). The majority (65.9%) preferred relying upon outcomes data as their learning style while 15.9% preferred opinion leader recommendations and 18.3% information about how the technology would affect practice efficiency. Factor analysis revealed four dimensions: Level of comfort with EHR; Concern over current ability to monitor medication adherence; Attitudes about value of DM applications; and Benefits vs cost of DM for payers. Women scored higher on attitudes about the value of digital applications (p<0.01). Providers who perceive non-adherence as costly, and those who believe DM could benefit providers and patients scored higher on the value of DM (p<.05). Those whose LSP focuses on improving efficiency and prescribers with a higher proportion of Medicaid/ uninsured patients displayed concern about their ability to monitor adherence (p<0.05). Willingness to be a Beta Test site for DM applications was positively correlated with concern about their ability to monitor adherence and attitudes about the value of DM (p <0.01).
Prescriber characteristics including LSP, focus on healthcare costs, and attitudes toward DM may be related to adoption of the IEM platform. Those with more Medicaid/ uninsured patients were more concerned about ability to monitor adherence while those focused-on cost and benefit to providers and patients viewed DM as part of a solution for managing outcomes and cost. Overall, LSP, patient panel size by payer type, and focus on healthcare cost containment should be considered when developing IEM provider training materials.
Otsuka Pharmaceutical Development & Commercialization, Inc.
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 impacts of the COVID-19 pandemic extend to global biodiversity and its conservation. Although short-term beneficial or adverse impacts on biodiversity have been widely discussed, there is less attention to the likely political and economic responses to the crisis and their implications for conservation. Here we describe four possible alternative future policy responses: (1) restoration of the previous economy, (2) removal of obstacles to economic growth, (3) green recovery and (4) transformative economic reconstruction. Each alternative offers opportunities and risks for conservation. They differ in the agents they emphasize to mobilize change (e.g. markets or states) and in the extent to which they prioritize or downplay the protection of nature. We analyse the advantages and disadvantages of these four options from a conservation perspective. We argue that the choice of post-COVID-19 recovery strategy has huge significance for the future of biodiversity, and that conservationists of all persuasions must not shrink from engagement in the debates to come.
In May 2019 the British School at Athens hosted an international conference on popular music of the Greek world. The conference aimed to explore and evaluate the diversity of Greek music apparent in the rich variety of local traditions and in the richness of urban popular music both established and emerging, and to examine its causes from broader musical, sociological and artistic perspectives. Rather than focus on particular forms, such as traditional folk music, rebetika, or the ‘new wave’ of the 1960s exemplified by the international success of composers such as Hadjidakis and Theodorakis, the conference set out to situate these traditions in a broader Greek context and also an explicitly international one, in this way building upon a growing trend (Bucuvalas 2019; Tragaki 2019).
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.