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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.
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.
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.
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.
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.
To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.
A pre- and postintervention, quasi-experimental quality improvement study.
Setting and participants:
Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.
We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014–January 2015) and the intervention period (April 2015–October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.
Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06–0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).
The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.
Precise radiocarbon (14C) dating of sedimentary sequences is important for developing robust chronologies of environmental change, but sampling of suitable components can be challenging in highly dynamic landscapes. Here we investigate radiocarbon determinations of different peat size fractions from six peat sites, representing a range of geomorphological contexts on the South Atlantic subantarctic islands of the Falklands and South Georgia. To investigate the most suitable fraction for dating, 112 measurements were obtained from three components within selected horizons: a fine fraction <0.2 mm, a coarse fraction >0.2 mm, and bulk material. We find site selection is critical, with locations surrounded by high-ground and/or relatively slowly accumulating sites more susceptible to the translocation of older carbon. Importantly, in locations with reduced potential for redeposition of material, our results show that there is no significant or systematic difference between ages derived from bulk material, fine or coarse (plant macrofossil) material, providing confidence in the resulting age model. Crucially, in areas comprising complex terrain with extreme relief, we recommend dating macrofossils or bulk carbon rather than a fine fraction, or employing comprehensive dating of multiple sedimentary fractions to determine the most reliable fraction(s) for developing a robust chronological framework.
Plant biodiversity is threatened by habitat loss, fragmentation and invasion by exotic species, but the effects of these disturbances on individual plant species are rarely quantified. Since the 1950s, brigalow Acacia harpophylla forests in Australia have been extensively cleared and converted to pastures dominated by exotic grasses. Here we assess the habitat requirements, population numbers and threats for four poorly known bush tomato species, Solanum adenophorum, Solanum dissectum, Solanum elachophyllum and Solanum johnsonianum. Herbarium records and surveys demonstrated a strong association of all four species with brigalow habitat, although S. elachophyllum also occurred in other habitat. We derived historical and current population estimates from plant densities at current sites and the area of mapped brigalow habitat. Density estimates are imprecise because the survey data vary greatly, but the assessment indicates the populations of all four species have declined > 93%. Solanum dissectum and S. johnsonianum did not persist in cleared brigalow habitat, whereas S. adenophorum and S. elachophyllum had some capacity to persist in clearings. None of the species occur where the exotic grass cover is > 40%. Between 27% and 57% of the records of the four species are in brigalow remnants with a high edge-to-area ratio or open canopy (< 50% cover), making them highly vulnerable to invasive grasses. We recommend the categorization of S. dissectum and S. johnsonianum as Critically Endangered, S. adenophorum as Vulnerable and S. elachophyllum as Near Threatened.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
The early and effective detection of neurocognitive disorders poses a key diagnostic challenge. We examined performance on common cognitive bedside tests according to differing delirium syndromal status and clinical (motor) subtypes in hospitalized elderly medical inpatients.
A battery of nine bedside cognitive tests was performed on elderly medical inpatients with DSM-IV delirium, subsyndromal delirium (SSD), and no delirium (ND). Patients with delirium were compared according to clinical (motor) subtypes.
A total of 198 patients (mean age 79.14 ± 8.26) were assessed with full syndromal delirium (FSD: n = 110), SSD (n = 45), and ND (n = 43). Delirium status was not associated with differences in terms of gender distribution, age, or overall medication use. Dementia burden increased with greater delirium status. Overall, the ability to meaningfully engage with the tests varied from 59% for the Vigilance B test to 85% for Spatial Span Forward test and was lowest in patients with FSD, where engagement ranged from 32% for the Vigilance B test to 77% for the Spatial Span Forwards test. The ND group was distinguished from SSD group for the Months of the year backwards, Vigilance B, global VSP, Clock Drawing test, and Interlocking Pentagons test. The SSD group was distinguished from the FSD group by Vigilance A, Spatial Span Forward, and Spatial Span Backwards. Regarding differences among motor subtypes in terms of percentage engagement and performance, the No subtype group had higher ratings across all tests. Delirious patients with no subtype had significantly lower scores on the DRS-R98 than for the other three subtype categories.
Simple bedside tests of attention, vigilance, and visuospatial ability are useful in distinguishing neurocognitive disorders, including SSD from other presentations.
Niemann–Pick type C (NP-C) disease is a rare neurodegenerative lysosomal storage disorder. It is highly heterogeneous, and there is limited awareness of a substantial subgroup that has an attenuated adolescent/adult-onset disease. In these patients psychiatric features, often a psychosis, may dominate the initial impression, although often there is an associated ataxia and cognitive impairment. Typically, patients experience a substantial diagnostic delay. In this review we highlight the importance of early recognition and discuss the pathophysiology, neuropsychiatric presentation and recent changes in the investigation and work-up of these patients, and treatment options.
The 13C/12C ratios of Upper Holocene benthic foraminiferal tests (genera Cibicides and Uvigerina) of deep sea cores from the various world ocean basins have been compared with those of the modern total carbon dioxide (TCO2) measured during the GEOSECS program. The δ13C difference between benthic foraminifera and TCO2 is 0.07 ± 0.04‰ for Cibicides and −0.83 ± 0.07‰ for Uvigerina at the 95% confidence level. δ13C analyses of the benthic foraminifera that lived during the last interglaciation (isotopic substage 5e, about 120,000 yr ago) show that the bulk of the TCO2 in the world ocean had a δ13C value 0.15 ± 0.12‰ lower than the modern one at the 95% confidence level, reflecting a depletion, compared to the present value, of the global organic carbon reservoir. Regional differences in δ13C between the various oceanic basins are explained by a pattern of deep water circulation different from the modern one: the Antarctic Bottom Water production was higher than today during the last interglaciation, but the eastward transport in the Circumpolar Deep Water was lower.
Field studies were conducted in 2000 and 2001 to evaluate corn yield-loss predictions generated by WeedSOFT, a computerized weed management decision aid. Conventional tillage practices were used to produce corn in 76-cm rows in Illinois, Indiana, Kansas, Michigan, Missouri, Nebraska, and Wisconsin. A total of 21 site-years from these seven states were evaluated in this study. At 4 wk after planting, weed densities and size, crop-growth stage, estimated weed-free yield, and environmental conditions at the time of application were entered into WeedSOFT to generate POST treatments ranked by percent maximum yield (PMY). POST treatments were chosen with yield losses ranging from 0 to 20%. Data were subjected to linear regression analysis by state and pooled over all states to determine the relationship between actual and predicted yield loss. A slope value equal to one implies perfect agreement between actual and predicted yield loss. Slope value estimates for Illinois and Missouri were equal to one. Actual yield losses were higher than the software predicted in Kansas and lower than predicted in Michigan, Nebraska, and Wisconsin. Slope value estimate from a data set containing all site years was equal to one. This research demonstrated that variability in yield-loss predictions occurred at sites that contained a high density of a single weed specie (>100/m2) regardless of its competitive index (CI); at sites with a predominant broadleaf weed with a CI greater than five, such as Palmer amaranth, giant ragweed, common sunflower, and common cocklebur; and at sites that experience moderate to severe drought stress.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Background: Cognitive Behavioural Therapy (CBT) aims to teach people skills to help them self-manage their depression. Trial evidence shows that CBT is an effective treatment for depression and individuals may experience benefits long-term. However, there is little research about individuals’ continued use of CBT skills once treatment has finished. Aims: To explore whether individuals who had attended at least 12 sessions of CBT continued to use and value the CBT skills they had learnt during therapy. Method: Semi-structured interviews were held with participants from the CoBalT trial who had received CBT, approximately 4 years earlier. Interviews were audio-recorded, transcribed and analysed thematically. Results: 20 participants were interviewed. Analysis of the interviews suggested that individuals who viewed CBT as a learning process, at the time of treatment, recalled and used specific skills to manage their depression once treatment had finished. In contrast, individuals who viewed CBT only as an opportunity to talk about their problems did not appear to utilize any of the CBT skills they had been taught and reported struggling to manage their depression once treatment had ended. Conclusions: Our findings suggest individuals may value and use CBT skills if they engage with CBT as a learning opportunity at the time of treatment. Our findings underline the importance of the educational model in CBT and the need to emphasize this to individuals receiving treatment.