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To compare patients treated for incomplete Kawasaki disease whose practitioners followed versus did not follow American Heart Association criteria and to evaluate the association of cardiology consultation with adherence to these guidelines.
Single centre retrospective cohort study of patients <18 years old who received ≥1 dose of intravenous immunoglobulin for Kawasaki disease between 01/2006 and 01/2018. We collected demographics, clinical and laboratory data, coronary artery abnormalities, and cardiology consultation status. Patients treated for incomplete Kawasaki disease were divided into two groups based on adherence versus nonadherence to American Heart Association guidelines and compared by Wilcoxon rank sum test and chi-squared or Fisher’s exact test.
Of the 357 patients treated for Kawasaki disease, 109 (31%) were classified as incomplete Kawasaki disease. The American Heart Association algorithm for identifying patients with incomplete Kawasaki disease was followed in 81/109 (74%). Coronary artery abnormalities were present in 46/109 (42%) of the patients who were treated for incomplete Kawasaki disease. Cardiology consultation was more frequent in those fulfilling American Heart Association criteria for the diagnosis of incomplete Kawasaki disease versus those who did not fulfill criteria (76% versus 48%, p = 0.005).
Over 25% of patients treated for incomplete Kawasaki disease did not meet American Heart Association guidelines. Guidelines were more frequently followed when the paediatric cardiology team was consulted. Consulting physicians with experience and expertise in the evaluation and management of incomplete KD should be strongly considered in the care of these patients.
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.
The COVID-19 pandemic emphasises the need to rethink and restructure the culture of healthcare organisations if we are to ensure the long-term well-being and mental health of healthcare provider organisations and their staff. In this paper, we recognise the high levels of stress and distress among staff of healthcare services before the COVID-19 pandemic began. We identify lessons for care of healthcare staff and illustrate the paths by which support mobilises and later deteriorates. Although this paper focuses on NHS staff in the UK, we contend that similar effects are likely in most healthcare systems.
The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.
Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.
Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.
Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.
King George Island (South Shetland Islands, Antarctic Peninsula) is renowned for its terrestrial palaeoenvironmental record, which includes evidence for potentially up to four Cenozoic glacial periods. An advantage of the glacigenic outcrops on the island is that they are associated with volcanic formations that can be isotopically dated. As a result of a new mapping and chronological study, it can now be shown that the published stratigraphy and ages of many geological units on eastern King George Island require major revision. The Polonez Glaciation is dated as c. 26.64 ± 1.43 Ma (Late Oligocene (Chattian Stage)) and includes the outcrops previously considered as evidence for an Eocene glacial ('Krakow Glaciation'). It was succeeded by two important volcanic episodes (Boy Point and Cinder Spur formations) formed during a relatively brief interval (< 2 Ma), which also erupted within the Oligocene Chattian Stage. The Melville Glaciation is dated as c. 21–22 Ma (probably 21.8 Ma; Early Miocene (Aquitanian Stage)), and the Legru Glaciation is probably ≤ c. 10 Ma (Late Miocene or younger). As a result of this study, the Polonez and Melville glaciations can now be correlated with increased confidence with the Oi2b and Mi1a isotope zones, respectively, and thus represent major glacial episodes.
New mapping and dating of volcanic outcrops on the east coast of Admiralty Bay, King George Island, has demonstrated that Eocene volcanic sequences are dominant and also crop out extensively elsewhere, particularly on the eastern part of the island. The sequences can be divided into at least three formations (Hennequin, Cape Vauréal and Carruthers Cliff) together with Eocene strata at Warkocz and near Lions Rump that are currently unassigned stratigraphically. New and recently published 40Ar/39Ar ages indicate that all of the formations are Early Eocene in age, mainly Ypresian, extending to Lutetian and possibly even Priabonian time in more easterly outcrops. Compositional contrasts exist between the groups (calc-alkaline vs tholeiitic). The formations are mainly composed of lavas, and many show evidence for contemporary inundation by water. They are interbedded with sedimentary rocks deposited mainly during flooding events as debris flows, debris avalanches, hyperconcentrated flows, from traction currents and in lakes. The common presence of juvenile volcanic detritus suggests that the sediments were probably linked to explosive hydrovolcanic eruptions, some of which were possibly rooted in summit ice caps. Other evidence is also permissive, but the presence of Eocene ice on King George Island is not well established at present.
Ethnohistoric accounts indicate that the people of Australia's Channel Country engaged in activities rarely recorded elsewhere on the continent, including food storage, aquaculture and possible cultivation, yet there has been little archaeological fieldwork to verify these accounts. Here, the authors report on a collaborative research project initiated by the Mithaka people addressing this lack of archaeological investigation. The results show that Mithaka Country has a substantial and diverse archaeological record, including numerous large stone quarries, multiple ritual structures and substantial dwellings. Our archaeological research revealed unknown aspects, such as the scale of Mithaka quarrying, which could stimulate re-evaluation of Aboriginal socio-economic systems in parts of ancient Australia.
The First Episode Rapid Early Intervention for Eating Disorders (FREED) service model is associated with significant reductions in wait times and improved clinical outcomes for emerging adults with recent-onset eating disorders. An understanding of how FREED is implemented is a necessary precondition to enable an attribution of these findings to key components of the model, namely the wait-time targets and care package.
This study evaluated fidelity to the FREED service model during the multicentre FREED-Up study.
Participants were 259 emerging adults (aged 16–25 years) with an eating disorder of <3 years duration, offered treatment through the FREED care pathway. Patient journey records documented patient care from screening to end of treatment. Adherence to wait-time targets (engagement call within 48 h, assessment within 2 weeks, treatment within 4 weeks) and care package, and differences in adherence across diagnosis and treatment group were examined.
There were significant increases (16–40%) in adherence to the wait-time targets following the introduction of FREED, irrespective of diagnosis. Receiving FREED under optimal conditions also increased adherence to the targets. Care package use differed by component and diagnosis. The most used care package activities were psychoeducation and dietary change. Attention to transitions was less well used.
This study provides an indication of adherence levels to key components of the FREED model. These adherence rates can tentatively be considered as clinically meaningful thresholds. Results highlight aspects of the model and its implementation that warrant future examination.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
Investigate an outbreak of coronavirus disease 2019 (COVID-19) among operating room staff utilizing contact tracing, mass testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and environmental sampling.
Operating room staff with positive SARS-CoV-2 molecular testing.
Epidemiologic and environmental investigations were conducted including contact tracing, environmental surveys, and sampling and review of the operating room schedule for staff-to-staff, staff-to-patient, and patient-to-staff SARS-CoV-2 transmission.
In total, 24 healthcare personnel (HCP) tested positive for SARS-CoV-2, including nurses (29%), surgical technologists (25%), and surgical residents (16%). Moreover, 19 HCP (79%) reported having used a communal area, most commonly break rooms (75%). Overall, 20 HCP (83%) reported symptomatic disease. In total, 72 environmental samples were collected from communal areas for SARS-CoV-2 genomic testing; none was positive. Furthermore, 236 surgical cases were reviewed for transmission: 213 (90%) had negative preoperative SARS-CoV-2 testing, 21 (9%) had a positive test on or before the date of surgery, and 2 (<1%) did not have a preoperative test performed. In addition, 40 patients underwent postoperative testing (mean, 13 days to postoperative testing), and 2 returned positive results. Neither of these 2 cases was linked to our outbreak.
Complacency in infection control practices among staff during peak community transmission of SARS-CoV-2 is believed to have driven staff-to-staff transmission. Prompt identification of the outbreak led to rapid interventions, ultimately allowing for uninterrupted surgical service.
Emerging from the warehouse of knowledge about terrestrial ecosystem functioning and the application of the systems ecology paradigm, exemplified by the power of simulation modeling, tremendous strides have been made linking the interactions of the land, atmosphere, and water locally to globally. Through integration of ecosystem, atmospheric, soil, and more recently social science interactions, plausible scenarios and even reasonable predictions are now possible about the outcomes of human activities. The applications of that knowledge to the effects of changing climates, human-caused nitrogen enrichment of ecosystems, and altered UV-B radiation represent challenges addressed in this chapter. The primary linkages addressed are through the C, N, S, and H2O cycles, and UV-B radiation. Carbon dioxide exchanges between land and the atmosphere, N additions and losses to and from lands and waters, early studies of SO2 in grassland ecosystem, and the effects of UV-B radiation on ecosystems have been mainstays of research described in this chapter. This research knowledge has been used in international and national climate assessments, for example the IPCC, US National Climate Assessment, and Paris Climate Accord. Likewise, the knowledge has been used to develop concepts and technologies related to sustainable agriculture, C sequestration, and food security.
This reflection article presents insights on conducting fieldwork during and after COVID-19 from a diverse collection of political scientists—from department heads to graduate students based at public and private universities in the United States and abroad. Many of them contributed to a newly published volume, Stories from the Field: A Guide to Navigating Fieldwork in Political Science (Krause and Szekely 2020). As in the book, these contributors draw on their years of experience in the field to identify the unique ethical and logistical challenges posed by COVID-19 and offer suggestions for how to adjust and continue research in the face of the pandemic’s disruptions. Key themes include how contingency planning must now be a central part of our research designs; how cyberspace has increasingly become “the field” for the time being; and how scholars can build lasting, mutually beneficial partnerships with “field citizens,” now and in the future.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
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 contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury.
Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score.
Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0–4) versus 0 (0–0), p = 0.02).
Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.
Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
Rapid spread of coronavirus disease 2019 (COVID-19) has affected people with intellectual disability disproportionately. Existing data does not provide enough information to understand factors associated with increased deaths in those with intellectual disability. Establishing who is at high risk is important in developing prevention strategies, given risk factors or comorbidities in people with intellectual disability may be different to those in the general population.
To identify comorbidities, demographic and clinical factors of those individuals with intellectual disability who have died from COVID-19.
An observational descriptive case series looking at deaths because of COVID-19 in people with intellectual disability was conducted. Along with established risk factors observed in the general population, possible specific risk factors and comorbidities in people with intellectual disability for deaths related to COVID-19 were examined. Comparisons between mild and moderate-to-profound intellectual disability subcohorts were undertaken.
Data on 66 deaths in individuals with intellectual disability were analysed. This group was younger (mean age 64 years) compared with the age of death in the general population because of COVID-19. High rates of moderate-to-profound intellectual disability (n = 43), epilepsy (n = 29), mental illness (n = 29), dysphagia (n = 23), Down syndrome (n = 20) and dementia (n = 15) were observed.
This is the first study exploring associations between possible risk factors and comorbidities found in COVID-19 deaths in people with intellectual disability. Our data provides insight into possible factors for deaths in people with intellectual disability. Some of the factors varied between the mild and moderate-to-profound intellectual disability groups. This highlights an urgent need for further systemic inquiry and study of the possible cumulative impact of these factors and comorbidities given the possibility of COVID-19 resurgence.
The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.7 times as many males as females. The disease became more common over the study period. Most cases (86%) were seen between March and July. Cerebrospinal fluid (CSF) was obtained from the cisterna magna in 77 dogs, the lumbar cistern in f5, and both sites in 3. Nucleated cell counts for 84 specimens ranged from 1 to 146 150 cells μL−1 (median 4500). Percentage eosinophils varied from 0 to 98% (median 83%). When both cisternal and lumbar CSF were collected, inflammation was more severe caudally. Seventy-three CSF specimens were subjected to enzyme-linked immunosorbent assay (ELISA) testing for antibodies against A. cantonensis; 61 (84%) tested positive, titres ranging from <100 to ⩾12 800 (median 1600). Sixty-one CSF specimens were subjected to real-time quantitative polymerase chain reaction (qPCR) testing using a new protocol targeting a bioinformatically-informed repetitive genetic target; 53/61 samples (87%) tested positive, CT values ranging from 23.4 to 39.5 (median 30.0). For 57 dogs, it was possible to compare CSF ELISA serology and qPCR. ELISA and qPCR were both positive in 40 dogs, in 5 dogs the ELISA was positive while the qPCR was negative, in 9 dogs the qPCR was positive but the ELISA was negative, while in 3 dogs both the ELISA and qPCR were negative. NA is an emerging infectious disease of dogs in Sydney, Australia.
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.