37 research outputs found

    Influence of Crohn’s disease related polymorphisms in innate immune function on ileal microbiome

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    We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome (“dysbiosis”) in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005–2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010–2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn’s colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6–12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.</div

    Search for the Epoch of Reionisation with HERA: Upper Limits on the Closure Phase Delay Power Spectrum

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    Radio interferometers aiming to measure the power spectrum of the redshifted 21 cm line during the Epoch of Reionisation (EoR) need to achieve an unprecedented dynamic range to separate the weak signal from overwhelming foreground emissions. Calibration inaccuracies can compromise the sensitivity of these measurements to the effect that a detection of the EoR is precluded. An alternative to standard analysis techniques makes use of the closure phase, which allows one to bypass antenna-based direction-independent calibration. Similarly to standard approaches, we use a delay spectrum technique to search for the EoR signal. Using 94 nights of data observed with Phase I of the Hydrogen Epoch of Reionization Array (HERA), we place approximate constraints on the 21 cm power spectrum at z=7.7z=7.7. We find at 95% confidence that the 21 cm EoR brightness temperature is \le(372)2^2 "pseudo" mK2^2 at 1.14 "pseudo" hh Mpc1^{-1}, where the "pseudo" emphasises that these limits are to be interpreted as approximations to the actual distance scales and brightness temperatures. Using a fiducial EoR model, we demonstrate the feasibility of detecting the EoR with the full array. Compared to standard methods, the closure phase processing is relatively simple, thereby providing an important independent check on results derived using visibility intensities, or related.Comment: 16 pages, 14 figures, accepted for publication by MNRA

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

    A new genus for Cirolana troglexuma Botosaneanu &amp; Iliffe, 1997, an anchialine cave dwelling cirolanid isopod (Crustacea, Isopoda, Cirolanidae) from the Bahamas

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    Cirolana troglexuma Botosaneanu &amp; Iliffe, 1997 is redescribed and a Lucayalana Bruce &amp; Brix, gen. n. established for the species. In total 38 specimens were collected from Hatchet Bay Cave, Eleuthera. Specimens on which previous records of L. troglexuma (from Exuma Cays, Cat Island, and Eleuthera) were based have been re-examined when possible. The diagnostic identifying characters and purported apomorphies for Lucayalana gen. n. are: frontal lamina short, narrow, less than 7% width of labrum, not extending to anterior margin of head; pleonite 3 extending posteriorly to posterior of pleonite 5, laterally overlapping pleonites 4 and 5; ventrally broad, forming a strong ventrally directed blade; pereopods 1–3 merus inferior margin RS not molariform. Mitochondrial COI and 16S loci and the nuclear 18S locus data show that all specimens are the one species. Comparison to additional cirolanid COI sequence data (BOLD, GenBank) show that Lucayalana troglexuma is genetically distinct to all other cirolanid genera with available COI sequences. The single male and females have shared COI (with three females), 16S (eight females) and 18S sequences (two females)

    A new genus for Cirolana troglexuma Botosaneanu & Iliffe, 1997, an anchialine cave dwelling cirolanid isopod (Crustacea, Isopoda, Cirolanidae) from the Bahamas

    No full text
    Cirolana troglexuma Botosaneanu & Iliffe, 1997 is redescribed and a Lucayalana Bruce & Brix, gen. n. established for the species. In total 38 specimens were collected from Hatchet Bay Cave, Eleuthera. Specimens on which previous records of L. troglexuma (from Exuma Cays, Cat Island, and Eleuthera) were based have been re-examined when possible. The diagnostic identifying characters and purported apomorphies for Lucayalana gen. n. are: frontal lamina short, narrow, less than 7% width of labrum, not extending to anterior margin of head; pleonite 3 extending posteriorly to posterior of pleonite 5, laterally overlapping pleonites 4 and 5; ventrally broad, forming a strong ventrally directed blade; pereopods 1–3 merus inferior margin RS not molariform. Mitochondrial COI and 16S loci and the nuclear 18S locus data show that all specimens are the one species. Comparison to additional cirolanid COI sequence data (BOLD, GenBank) show that Lucayalana troglexuma is genetically distinct to all other cirolanid genera with available COI sequences. The single male and females have shared COI (with three females), 16S (eight females) and 18S sequences (two females)

    A new genus for Cirolana troglexuma Botosaneanu & Iliffe, 1997, an anchialine cave dwelling cirolanid isopod (Crustacea, Isopoda, Cirolanidae) from the Bahamas

    No full text
    Cirolana troglexuma Botosaneanu & Iliffe, 1997 is redescribed and a Lucayalana Bruce & Brix, gen. n. established for the species. In total 38 specimens were collected from Hatchet Bay Cave, Eleuthera. Specimens on which previous records of L. troglexuma (from Exuma Cays, Cat Island, and Eleuthera) were based have been re-examined when possible. The diagnostic identifying characters and purported apomorphies for Lucayalana gen. n. are: frontal lamina short, narrow, less than 7% width of labrum, not extending to anterior margin of head; pleonite 3 extending posteriorly to posterior of pleonite 5, laterally overlapping pleonites 4 and 5; ventrally broad, forming a strong ventrally directed blade; pereopods 1–3 merus inferior margin RS not molariform. Mitochondrial COI and 16S loci and the nuclear 18S locus data show that all specimens are the one species. Comparison to additional cirolanid COI sequence data (BOLD, GenBank) show that Lucayalana troglexuma is genetically distinct to all other cirolanid genera with available COI sequences. The single male and females have shared COI (with three females), 16S (eight females) and 18S sequences (two females)
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