22 research outputs found
Correction to: European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention (Journal of Headache and Pain (2019) 20:6 DOI: 10.1186/s10194-018-0955-y)
No full textFollowing publication of the original article [1], the authors notified us of some misreported data due to the publication of the EVOLVE-2 trial (Cephalalgia. 2018;38:1442-1454), which substantially changed the level of evidence of galcanezumab for the prevention of episodic migraine. All changes are marked in bold and with red in Figure 1 and Figure 2. Please note that the final recommendations remain unchanged. Reference #51 was added: Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim B-K, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38:1442-1454. Please find below the updated text, tables, and figures. Results We identified 29 studies eligible to be considered in the present guidelines (Fig. 1) [23-51]. Fifteen of the selected studies (Tables 1 and 2) were phase II or III randomized clinical trials (RCTs) reporting data on safety or efficacy of the CGRP mAbs [26,27,31-36,41-45,50,51]; 14 additional studies were post-hoc or pooled analyses from the RCTs, open label-extension of the RCTs, or open label studies [23-25,28-30,37-40,46-49]. Risk of bias summary for the selected studies is reported in Fig. 2. Certainty assessment of outcomes for studies in EM and CM is reported in Tables 3 and 4. Recommendations related to the use of CGRP mAbs for prevention of EM and CM are reported in Table 5. PICO question 1: In patients with EM, is preventive treatment with CGRP mAbs as compared to placebo, effective and safe? Population: patients with EM Intervention: any preventive CGRP mAb Comparison: placebo Outcome: reduction in days of migraine or headache, reduction in the use of acute attack medication, improvement in function, responder ratio (patients with > 50% reduction in migraine or headache days), serious adverse events (SAEs), mortality (grade of importance: critical) Analysis of evidence We found 15 eligible studies which evaluated whether treatment with CGRP mAbs as compared to placebo is effective and safe [26,27,31-36,41-45,50,51]. Among the eligible studies one was on eptinezumab [32], five studies on erenumab [35,36,44,45,50], four studies on fremanezumab [26,27,34,41], and five studies on galcanezumab [31,33,42,43]. One phase IIIb study on erenumab was not included in the PICO question 1 because it included only patients with previous drug failure [50]. Eptinezumab Summary of findings for treatment with eptinezumab quarterly injection compared with placebo for prevention of EM is provided in Table 6. (Figure presented). © 2019 The Author(s)
CLEAR: The Ionization and Chemical-enrichment Properties of Galaxies at 1.1 < z < 2.3
No full textWe use deep spectroscopy from the Hubble Space Telescope Wide-Field-Camera 3 IR grisms combined with broadband photometry to study the stellar populations, gas ionization and chemical abundances in star-forming galaxies at z ∼ 1.1-2.3. The data stem from the CANDELS Lyα Emission At Reionization (CLEAR) survey. At these redshifts, the grism spectroscopy measure the [O II] λ λ3727, 3729, [O III]λ λ4959, 5008, and Hβ strong emission features, which constrain the ionization parameter and oxygen abundance of the nebular gas. We compare the line-flux measurements to predictions from updated photoionization models (MAPPINGS V; Kewley et al.), which include an updated treatment of nebular gas pressure, log P / k = n e T e . Compared to low-redshift samples (z ∼ 0.2) at fixed stellar mass, log M * / M ⊙ = 9.4-9.8, the CLEAR galaxies at z = 1.35 (1.90) have lower gas-phase metallicity, Δ ( log Z ) = 0.25 (0.35) dex, and higher ionization parameters, Δ ( log q ) = 0.25 (0.35) dex, where U ≡ q/c. We provide updated analytic calibrations between the [O III], [O II], and Hβ emission-line ratios, metallicity, and ionization parameter. The CLEAR galaxies show that at fixed stellar mass, the gas ionization parameter is correlated with the galaxy specific star formation rates, where Δ log q ≃ 0.4 × Δ ( log sSFR ) , derived from changes in the strength of galaxy Hβ equivalent width. We interpret this as a consequence of higher gas densities, lower gas covering fractions, combined with a higher escape fraction of H-ionizing photons. We discuss both tests to confirm these assertions and implications this has for future observations of galaxies at higher redshifts. © 2022. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Detailed Study of Stars and Gas in a z = 8.3 Massive Merger with Extreme Dust Conditions
No full textWe present galaxy MACS0416-Y1 at z _spec = 8.312 as observed by the CAnadian NIRISS Unbiased Cluster Survey. MACS0416-Y1 has been shown to have extreme dust properties; thus, we study the physical properties and star formation histories of its resolved components. Overall, we find that MACS0416-Y1 is undergoing a star formation burst in three resolved clumps. The central clump is less massive compared to the other clumps and possibly formed in the merging process of the two larger clumps. Although the star formation history indicates an ongoing star formation burst, this gas-rich galaxy shows comparable star formation efficiency to cosmic noon galaxies. Using NIRSpec prism spectroscopy, we measure metallicity, , ionization parameter, , and electron temperature T _e = 18000 ± 4000 K. The emission line ratios of the galaxy indicate an evolved interstellar medium similar to z ∼ 2 star-forming galaxies. Further, we find possible presence of ionization from an active galactic nucleus (AGN) using emission line diagnostics; however, we do not detect a broad-line component in the H β emission line. As this gas-rich galaxy is undergoing a major merger, we hypothesize that the high dust temperature in MACS0416-Y1 is caused by the star formation burst or a possible narrow-line AGN
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
No full textThe combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
The Vascular Interventions and Surgery in Trauma Audit (VISTA): A Prospective National Service Evaluation of Vascular Trauma in the UK
No full text\ua9 2025 The Author(s). Objective: The frequency, operative management, and outcomes for patients with traumatic vascular injury in the UK are unknown. The Vascular Interventions and Surgery in Trauma Audit (VISTA) aimed to describe the contemporary landscape of UK vascular trauma compared with retrospective data from the National Vascular Registry (NVR). Methods: A prospective, resident led service evaluation was conducted across UK major trauma centres (MTCs) delivered by the National Trauma and Research Innovation Collaborative and the Vascular and Endovascular Research Network. The evaluation included patients with traumatic injuries to named vessels falling under the management remit of vascular surgery, identified radiologically or intra-operatively, between March and October 2022 and comparative NVR data from 2017 to 2022. Results: VISTA captured 302 patients with 339 vascular injuries from 27 MTCs. The median patient age was 41 years (interquartile range 26, 59) and 78.8% (n = 238) were men. Most injuries resulted from road traffic collisions (42.4%, n = 128). Overall, 38 patients (12.6%) were shocked on arrival at the emergency department. Two thirds of patients (65.6%, n = 198) required surgery, of whom 140 (70.7%) had an open procedure and 58 (29.3%) an endovascular intervention. Open procedures included 86 (61.4%) extremity interventions (including six [4.3%] primary amputations), four (2.9%) carotid repairs, four (2.9%) caval repairs, and two (1.5%) aortic repairs. Endovascular procedures included 23 (40%) thoracic endovascular aortic repairs, two (3%) extremity stents, and one (2%) extremity embolisation. The secondary amputation rate was 12% (10 of 86). Extrapolated annual VISTA data suggest the NVR fails to capture 58% of aortic injuries and 42% of extremity vascular injuries requiring intervention. Conclusion: UK wide registries do not accurately capture surgical volume and outcomes for vascular interventions following trauma. Granular national datasets are required to establish evidence based key performance indicators for life and limb salvage following vascular trauma to improve services, promote safety, and assure patient outcomes
Genetic mechanisms of critical illness in COVID-19.
No full textHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Gene expression studies of lytic infection and chromosomal integration of human herpesvirus 6.
No full textHuman herpesvirus 6 (HHV-6) was discovered in 1986 in patients with lymphoproliferative diseases and it has a predominant tropism for CD4+ T cells in vitro and in vivo. The virus can be divided into two variants: HHV-6A and 6B, based on the differences in biological properties and DNA sequences. HHV-6B has been shown to be the causative agent of exanthem subitum while HHV-6A has no clear association with any disease yet. The genome for both variants has been defined and each encodes just over 100 open readings frames (ORFs). However, there is limited knowledge regarding the functions and transcription kinetics of most ORFs. This thesis discusses the development of DNA microarrays for HHV-6 and the application of the arrays to characterise HHV-6B gene expression in the SupT1 cell line. The expression pattern of individual viral genes over a 60h time course (<1 replication cycle) was profiled. Viral genes were further classified into three kinetic groups: immediately-early (IE), early (E), and late (L), according to their transcriptional activity in the absence of de novo protein synthesis or DNA replication. In addition, HHV-6 presents an atypical stage in the herpesvirus life cycle in which the viral genome is integrated into host chromosomes. The prevalence of HHV-6 integration was estimated to be between 0.21% to 3%. An individual harbouring integrated HHV-6 was previously identified. The molecular biology and gene expression of this integrated HHV-6 DNA were characterised. Expression of viral genes belonging to all three kinetic classes (IE, E, and L) was detected in vitro and ex vivo. The data strongly suggest that the chromosomal HHV-6 sequence is transcriptionally active and the implications of this are discussed
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Dusty Starbursts Masquerading as Ultra-high Redshift Galaxies in JWST CEERS Observations
No full textLyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts (z ≲ 7) may also mimic the near-infrared (near-IR) colors of z > 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6σ SCUBA-2 detection at 850 μm around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4-6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations. © 2023. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
The GOGREEN and GCLASS surveys : first data release
No full textWe present the first public data release of the GOGREEN (Gemini Observations of Galaxies in Rich Early Environments) and GCLASS (Gemini CLuster Astrophysics Spectroscopic Survey) surveys of galaxies in dense environments, spanning a redshift range 0.8 <z <1.5. The surveys consist of deep, multiwavelength photometry and extensive Gemini GMOS spectroscopy of galaxies in 26 overdense systems ranging in halo mass from small groups to the most massive clusters. The objective of both projects was primarily to understand how the evolution of galaxies is affected by their environment, and to determine the physical processes that lead to the quenching of star formation. There was an emphasis on obtaining unbiased spectroscopy over a wide stellar mass range (M greater than or similar to 2 x 10(10) M-circle dot), throughout and beyond the cluster virialized regions. The final spectroscopic sample includes 2771 unique objects, of which 2257 have reliable spectroscopic redshifts. Of these, 1704 have redshifts in the range 0.8 <z <1.5, and nearly 800 are confirmed cluster members. Imaging spans the full optical and near-infrared wavelength range, at depths comparable to the UltraVISTA survey, and includes Hubble Space Telescope/Wide Field Camera 3 F160W (GOGREEN) and F140W (GCLASS). This data release includes fully reduced images and spectra, with catalogues of advanced data products including redshifts, line strengths, star formation rates, stellar masses, and rest-frame colours. Here, we present an overview of the data, including an analysis of the spectroscopic completeness and redshift quality.Peer reviewe
