Subclinical infection and asymptomatic carriage of gastrointestinal zoonoses: Occupational exposure, environmental pathways, and the anonymous spread of disease

Asymptomatic carriage of gastrointestinal zoonoses is more common in people whose profession involves them working directly with domesticated animals. Subclinical infections (defined as an infection in which symptoms are either asymptomatic or sufficiently mild to escape diagnosis) are important within a community as unknowing (asymptomatic) carriers of pathogens do not change their behaviour to prevent the spread of disease; therefore the public health significance of asymptomatic human excretion of zoonoses should not be underestimated. However, optimal strategies for managing diseases where asymptomatic carriage instigates further infection remain unresolved, and the impact on disease management is unclear. In this review we consider the environmental pathways associated with prolonged antigenic exposure and critically assess the significance of asymptomatic carriage in disease outbreaks Although screening high-risk groups for occupationally acquired diseases would be logistically problematical, there may be an economic case for identifying and treating asymptomatic carriage if the costs of screening and treatment are less than the costs of identifying and treating those individuals infected by asymptomatic hosts

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Accommodation-based coal cycles and significant surface correlation of low-accommodation lower cretaceous coal seams, Lloydminster heavy oil field, Alberta, Canada: implications for coal quality distribution

Sequence stratigraphy and coal cycles based on accommodation trends were investigated in the coal-bearing Lower Cretaceous Mannville Group in the Lloydminster heavy oil field, eastern Alberta. The study area is in a low accommodation setting on the cratonic margin of the Western Canada sedimentary basin. Geophysical log correlation of coal seams, shoreface facies, and the identification of incised valleys has produced a sequence-stratigraphic framework for petrographic data from 3 cored and 115 geophysical-logged wells. Maceral analysis, telovitrinite reflectance, and fluorescence measurements were taken from a total of 206 samples. Three terrestrial depositional environments were interpreted from the petrographic data: ombrotrophic mire coal, limnotelmatic mire coal, and carbonaceous shale horizons. Accommodation-based coal (wetting- and drying-upward) cycles represent trends in depositional environment shifts, and these cycles were used to investigate the development and preservation of the coal seams across the study area. The low-accommodation strata are characterized by a high-frequency occurrence of significant surfaces, coal seam splitting, paleosol, and incised-valley development. Three sequence boundary unconformities are identified in only 20 m (66 ft) of strata. Coal cycle correlations illustrate that each coal seam in this study area was not produced by a single peat-accumulation episode but as an amalgamation of a series of depositional events. Complex relations between the Cummings and Lloydminster coal seams are caused by the lateral fragmentation of strata resulting from the removal of sediment by subaerial erosion or periods of nondeposition. Syndepositional faulting of the underlying basement rock changed local accommodation space and increased the complexity of the coal cycle development. This study represents a low-accommodation example from a spectrum of stratigraphic studies that have been used to establish a terrestrial sequence-stratigraphic model. The frequency of changes in coal seam quality is an important control on methane distribution within coalbed methane reservoirs and resource calculations in coal mining. A depositional model based on the coal cycle correlations, as shown by this study, can provide coal quality prediction for coalbed methane exploration, reservoir completions, and coal mining

Geology and Geochemistry of the Hydrocarbon Compositional Changes in the Triassic Montney Formation, Western Canada

The geochemistry of produced fluids has been investigated in the Triassic Montney Formation in the Western Canadian Sedimentary Basin (WCSB). Understanding the geochemistry of produced fluids is a valuable tool in the exploration and development of a complex petroleum system such as the Montney Formation. The petroleum system changes from in situ unconventional reservoirs in the west to more conventional reservoirs that contain migrated hydrocarbons to the east. The workflow of basin modeling and mapping of isomer ratio calculations for butane and pentane as well as the mapping of excess methane percentage was used to highlight areas of gas compositional changes in the Montney Formation play area. This workflow shows the migration of hydrocarbons from deeper, more mature areas to less mature areas in the east through discrete pathways. Methane has migrated along structural elements such as the Fort St. John Graben as well as areas that have seen changes in higher permeability lithologies (i.e., well 14-23-74-8W6M). Excess methane percentage calculations highlight changes due to fluid mixing from hydrocarbon migration. The regional maturation polynomial regression line was used to determine the gas dryness percentage for each well on the basis of its maturation level determined by the butane isomer ratio. The deviation from the calculated gas dryness according to the regression was determined as an excess methane percentage. The British Columbia (BC) Montney play appears to have hydrocarbon compositions that reflect an in situ generation, while the Montney play in Alberta (AB) has a higher proportion of its hydrocarbon volumes from migrated hydrocarbons. The workflow provides a better understanding of the hydrocarbon system to optimize operations and increase production efficiency. Understanding the distribution of gas compositions within a play area will provide key information on the liquid and gas phases present and an understanding of how gas composition may change over the well life, as well as helping to maximize liquid recovery during well operations.Science, Faculty ofNon UBCEarth, Ocean and Atmospheric Sciences, Department ofReviewedFacultyResearcherGraduat

Supporting formation and operation of virtual organisations in a grid environment

The ability to create reliable and scalable virtual organisations (VOs) on demand in a dynamic, open and competitive environment is one of the challenges that underlie the Grid concept and research. In this paper, we describe the agent-based mechanisms that we are currently developing within the CONOISE and CONOISE-G projects for supporting VO formation and operation