SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Khatri G.) "

Search: WFRF:(Khatri G.)

  • Result 1-50 of 59
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
  •  
2.
  • 2021
  • swepub:Mat__t
  •  
3.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
  •  
4.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
  •  
5.
  • 2021
  • swepub:Mat__t
  •  
6.
  •  
7.
  •  
8.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
  •  
9.
  •  
10.
  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
  •  
11.
  •  
12.
  • Drake, TM, et al. (author)
  • Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
  • 2020
  • In: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
  • Journal article (peer-reviewed)abstract
    • Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
  •  
13.
  •  
14.
  • Loza, M. J., et al. (author)
  • Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
  • 2016
  • In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
  • Journal article (peer-reviewed)abstract
    • Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
  •  
15.
  •  
16.
  •  
17.
  •  
18.
  • Adlarson, Patrik, et al. (author)
  • Search for eta-mesic He-4 in the dd -> (3)Hen pi(0) and dd -> (3)Hep pi(-) reactions with the WASA-at-COSY facility
  • 2017
  • In: Nuclear Physics A. - : ELSEVIER SCIENCE BV. - 0375-9474 .- 1873-1554. ; 959, s. 102-115
  • Journal article (peer-reviewed)abstract
    • The search for He-4-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd -> (3)Hen pi(0) and dd -> (3)Hep pi(-) processes. The deuteron beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd -> He-4 eta reaction ranging from Q = 70 MeV to Q = 30 MeV. The luminosity was determined based on the dd -> (3)Hen reaction and the quasi-free proton proton scattering via dd -> ppn(spectator)n(spectator) reactions. The excitation functions, determined independently for the measured reactions, do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd -> (4He-eta)(bound) -> (3)Hen pi(0) and dd -> (He-4-eta)(bound) -> (3)Hep pi(-) processes were determined taking into account the isospin relation between the both of the considered channels. The results of the analysis depend on the assumptions of the N* (1535) momentum distribution in the anticipated mesic-He-4. Assuming, as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in He-4, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for n pi(0) and p pi(-) channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-He-3 nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for n pi(0) and p pi(-) channels respectively. (C) 2017 Elsevier B.V. All rights reserved.
  •  
19.
  •  
20.
  • Adlarson, Patrik, et al. (author)
  • Backward single-pion production in the pd -> He-3 pi(0)reaction with WASA-at-COSY
  • 2018
  • In: European Physical Journal A. - : SPRINGER. - 1434-6001 .- 1434-601X. ; 54:9
  • Journal article (peer-reviewed)abstract
    • New data on the production of single neutral pions in the pd -> He-3 pi(0) reaction are presented. For fifteen proton beam momenta between p(p) = 1.60GeV/c and p(p) = 1.74 GeV/c, differential cross sections are determined over a large fraction of the backward hemisphere. Since the only previous systematic measurements of single-pion production at these energies were made in collinear kinematics, the present work constitutes a significant extension of the current knowledge on this reaction. Even this far above the production threshold, significant changes are found in the behaviour of the angular distributions over small intervals in beam momentum.
  •  
21.
  • Adlarson, Patrik, et al. (author)
  • Importance of d-wave contributions in the charge symmetry breaking reaction dd -> He-4 pi(0)
  • 2018
  • In: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 781, s. 645-650
  • Journal article (peer-reviewed)abstract
    • This letter reports a first quantitative analysis of the contribution of higher partial waves in the charge symmetry breaking reaction dd -> He-4 pi(0) using the WASA-at-COSY detector setup at an excess energy of Q = 60 MeV. The determined differential cross section can be parametrized as d sigma/d Omega = a + b cos(2) theta*, where theta* is the production angle of the pion in the center-of-mass coordinate system, and the results for the parameters are a = (1.55 +/- 0.46(stat)(-0.8)(+0.32)(syst)) pb/sr and b = (13.1 +/- 2.1(stat)(-2.7)(+1.0)(syst)) pb/sr. The data are compatible with vanishing p-waves and a sizable d-wave contribution. This finding should strongly constrain the contribution of the A isobar to the dd -> He-4 pi(0) reaction and is, therefore, crucial for a quantitative understanding of quark mass effects in nuclear production reactions.
  •  
22.
  • Adlarson, Patrik, et al. (author)
  • Isoscalar single-pion production in the region of Roper and d*(2380) resonances
  • 2017
  • In: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 774, s. 599-607
  • Journal article (peer-reviewed)abstract
    • Exclusive measurements of the quasi-free pn -> pp pi(-) and pp -> pp pi(0) reactions have been performed by means of pd collisions at T-p= 1.2 GeV using the WASA detector setup at COSY. Total and differential cross sections have been obtained covering the energy region T-p= 0.95-1.3 GeV (root s = 2.3-2.46 GeV), which includes the regions of triangle(1232), N*(1440) and d*(2380) resonance excitations. From these measurements the isoscalar single-pion production has been extracted, for which data existed so far only below T-p = 1 GeV. We observe a substantial increase of this cross section around 1 GeV, which can be related to the Roper resonance N*(1440), the strength of which shows up isolated from the triangle resonance in the isoscalar (N pi)(I=0) invariant-mass spectrum. No evidence for a decay of the dibaryon resonance d*(2380) into the isoscalar (NN pi)(I=0) channel is found. An upper limit of 180 mu b (90% CL.) corresponding to a branching ratio of 9% has been deduced.
  •  
23.
  • Adlarson, Patrik, et al. (author)
  • Measurement of the (n)over-right-arrowp -> d pi(0) pi(0) reaction with polarized beam in the region of the d(*)(2380) resonance
  • 2016
  • In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 52:5, s. 1-7
  • Journal article (peer-reviewed)abstract
    • We report on a high-statistics measurement of the most basic double-pionic fusion reaction over the energy region of the d (*)(2380) resonance by use of a polarized deuteron beam and observing the double fusion reaction in the quasifree scattering mode. The measurements were performed with the WASA detector setup at COSY. The data reveal substantial analyzing powers and confirm conclusions about the d(*) resonance obtained from unpolarized measurements. We also confirm the previous unpolarized data obtained under complementary kinematic conditions.
  •  
24.
  • Adlarson, Patrik, et al. (author)
  • Measurement of the ω → π+π−π0 Dalitz plot distribution : The WASA-at-COSY Collaboration
  • 2017
  • In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 770, s. 418-425
  • Journal article (peer-reviewed)abstract
    • Using the production reactions pd -> He-3 omega and pp -> pp omega, the Dalitz plot distribution for the omega -> pi(+)pi(-)pi(0)decay is studied with the WASA detector at COSY, based on a combined data sample of (4.408 +/- 0.042) x 10(4) events. The Dalitz plot density is parametrised by a product of the P-wave phase space and a polynomial expansion in the normalised polar Dalitz plot variables Z and phi. For the first time, a deviation from pure P-wave phase space is observed with a significance of 4.1 sigma. The deviation is parametrised by a linear term 1+2 alpha Z, with alpha determined to be +0.147 +/- 0.036, consistent with the expectations of rho-meson-type final-state interactions of the P-wave pion pairs. (C) 2017 The Author. Published by Elsevier B.V.
  •  
25.
  • Adlarson, Patrik, et al. (author)
  • Measurements of branching ratios for eta decays into charged particles
  • 2016
  • In: PHYSICAL REVIEW C. - 2469-9985. ; 94:6
  • Journal article (peer-reviewed)abstract
    • The WASA-at-COSY experiment has collected 3 x 10(7) events with eta mesons produced via the reaction pd -> He-3 eta at T = 1.0 GeV. Using this data set, we evaluate the branching ratios of the decays eta -> pi(+)pi(-)gamma, eta -> e(+)e(-)gamma, eta -> pi(+)pi(-)e(+)e(-), and eta -> e(+)e(-)e(+)e(-). The branching ratios are normalized to the eta -> pi(+)pi(-) pi(0) decay. In addition an upper limit on a CP-violating asymmetry in eta -> pi(+)pi(-)e(+)e(-) is extracted.
  •  
26.
  • Adlarson, Patrik, et al. (author)
  • Search for an isospin I=3 dibaryon
  • 2016
  • In: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 762, s. 455-461
  • Journal article (peer-reviewed)abstract
    • Various theoretical calculations based on QCD or hadronic interactions predict that in addition to the recently observed dibaryon resonance d*(2380) with I(J(P)) = 3(0(+)) there should also exist a dibaryon resonance with mirrored quantum numbers I(J(P)) = 3(0(+)). We report here on a search for such a NN-decoupled state in data on the pp -> pp pi(+) pi(+) pi(-) pi(-) reaction. Since no clear-cut evidence has been found, we give upper limits for the production cross section of such a resonance in the mass range 2280-2500 MeV.
  •  
27.
  • Adlarson, Patrik, et al. (author)
  • Search for C violation in the decay eta -> pi(0)e(+)e(-) with WASA-at-COSY
  • 2018
  • In: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 784, s. 378-384
  • Journal article (peer-reviewed)abstract
    • We report on the search for the rare decay eta -> pi(0)e(+)e(-) which is of interest to study C violation in the electromagnetic interaction which would indicate contributions from physics beyond the Standard Model, since the allowed decay via a two-photon intermediate state is strongly suppressed. The experiment has been performed using the WASA-at-COSY installation, located at the COSY accelerator of the Forschungszentrum Julich, Germany. In total 3 x 10(7) events of the reaction pd -> He-3 eta have been recorded at an excess energy of Q = 59.8MeV. Based on this data set the C parity violating decay eta -> pi(0)gamma* -> pi(0)e(+)e(-) via a single-photon intermediate state has been searched for, resulting in new upper limits of Gamma(eta -> pi(0)e(+) e(-))/Gamma(eta -> pi(+) pi(-) pi(0)) < 3.28 x 10(-5) and Gamma(eta -> pi(0)e(+) e(-))/Gamma(eta -> all)< 7.5 x 10(-6) (CL=90%), respectively. 
  •  
28.
  • Adlarson, Patrik, et al. (author)
  • Spin Dependence of eta Meson Production in Proton-Proton Collisions Close to Threshold
  • 2018
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 120:2
  • Journal article (peer-reviewed)abstract
    • Taking advantage of the high acceptance and axial symmetry of the WASA-at-COSY detector, and the high polarization degree of the proton beam of COSY, the reaction →pp→ppη has been measured close to threshold to explore the analyzing power Ay. The angular distribution of Ay is determined with the precision improved by more than 1 order of magnitude with respect to previous results, allowing a first accurate comparison with theoretical predictions. The determined analyzing power is consistent with zero for an excess energy of Q=15  MeV, signaling s-wave production with no evidence for higher partial waves. At Q=72  MeV the data reveal strong interference of Ps and Pp partial waves and cancellation of (Pp)2 and Ss∗Sd contributions. These results rule out the presently available theoretical predictions for the production mechanism of the η meson.
  •  
29.
  • Adlarson, Patrik, et al. (author)
  • Total and differential cross sections of η-production in proton–deuteron fusion for excess energies between Qη = 13 MeV and Qη = 81 MeV
  • 2018
  • In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 782, s. 297-304
  • Journal article (peer-reviewed)abstract
    • New data on both total and differential cross sections of the production of eta mesons in proton-deuteron fusion to He-3 eta in the excess energy region 13.6 MeV <= Q(eta) <= 80.9 MeV are presented. These data have been obtained with the WASA-at-COSY detector setup located at the Forschungszentrum Julich, using a proton beam at 15 different beam momenta between p(p) = 1.60 GeV/c and p(p) = 1.74 GeV/c. While significant structure of the total cross section is observed in the energy region 20 MeV less than or similar to Q(eta) less than or similar to 60 MeV, a previously reported sharp variation around Q(eta) approximate to 50 MeV cannot be confirmed. Angular distributions show the typical forward- peaking that was noted earlier. For the first time, it is possible to study the development of these angular distributions with rising excess energy over a wide interval.
  •  
30.
  •  
31.
  •  
32.
  •  
33.
  •  
34.
  •  
35.
  • Khatri, B., et al. (author)
  • Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
  • 2022
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
  •  
36.
  • Lindgren, Arne G., et al. (author)
  • International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery
  • 2022
  • In: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 17:3, s. 260-268
  • Journal article (peer-reviewed)abstract
    • Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.
  •  
37.
  • Nguyen, Thanh N, et al. (author)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • In: Neurology. - 1526-632X. ; 100:4
  • Journal article (peer-reviewed)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
  •  
38.
  • Shoamanesh, Ashkan, et al. (author)
  • Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke) : an international, randomised, double-blind, placebo-controlled, phase 2b trial
  • 2022
  • In: The Lancet. - 0140-6736. ; 400:10357, s. 997-1007
  • Journal article (peer-reviewed)abstract
    • Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.
  •  
39.
  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
  •  
40.
  • Aghakhanian, F, et al. (author)
  • INTEGRATION OF GWAS AND EPIGENETIC STUDIES IDENTIFIES NOVEL GENES THAT ALTER EXPRESSION IN THE MINOR SALIVARY GLAND IN SJOGREN'S DISEASE
  • 2022
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 72-73
  • Conference paper (other academic/artistic)abstract
    • Sjogren’s disease (SjD) is an autoimmune disease characterized by reduced function of exocrine glands (i.e., salivary and lacrimal glands). Epithelial cell damage resulting from lymphocytic infiltration has been implicated in SjD etiology [1]. How genetic and epigenetic changes influence epithelial-immune cell interactions in SjD pathogenesis remain understudied.ObjectivesEvaluate the role of SjD risk loci in salivary gland tissue to gain insights into the potential genes involved in salivary gland dysfunction.MethodsSNPs from 16 regions with SNP-SjD associations (P<5x10-8) in our GWAS study (3232 SjD cases) and meta-analysis of ImmunoChip data (619 SjD cases) [2] were interrogated for eQTLs using Genotype-Tissue Expression (GTEx) minor salivary gland data. Subsequent analysis identified genes that were both eQTLs in the minor salivary gland and significantly expressed in RNA-seq and ATAC-seq data from the submaxillary salivary gland epithelial cell line, A253. Pathway enrichment analysis was performed using gProfiler on the genes where coalescence of eQTL, RNA-seq, and ATAC-seq data was observed. To further validate the results, we performed transcriptome-wide association study (TWAS) analysis using GWAS summary statistics and minor salivary gland eQTL GTEx data.ResultsIn total, 5884 genome-wide significant SNPs from 16 SjD risk loci were identified as potential minor salivary gland eQTLs using two discovery thresholds: p(FDR)<0.05 provided by eQTL study (3566 SNPs) and p(FDR)>0.05 and p<0.05 in eQTL study (2318 SNPs). Further analysis revealed 10 SjD risk loci with SNPs that were minor salivary gland eQTLs for a total of 155 unique genes that had a coalescence of RNA- and ATAC-seq data in A253 cells. Many SNPs altered the expression of the nearest gene to the risk allele (i.e., index gene), such as IRF5 and TNPO3 on chromosome 7 at 128Mb; however, this locus had 12 additional genes that were eQTLs in minor salivary gland. In contrast, other loci had no reported eQTLs for the index gene, but several reported eQTLs for other genes, such TYK2 on chromosome 19 at 10Mb that showed no change in TYK2 expression but eQTLs for 8 distant genes, including ICAM1. Pathway enrichment analysis revealed an enrichment in Butyrophilin (BTN) family interactions (R-HSA-8851) (PAdj=1.564x10-5), including the BTN2A1, BTN2A2, BTN3A1, BTN3A2 and BTN3A3 gene cluster in the MHC region. In further support, TWAS of the minor salivary gland and the SjD GWAS summary statistics (after Bonferroni correction) showed association between SjD and BTN3A2 (p=1.24x10-42), as well as many other loci in the MHC region. In addition, several long non-coding (lnc) RNAs on chromosome 17 were significant, peaking at RP11-259G18.1 (p=4.43x10-10).ConclusionThis study shows that SjD-associated risk alleles influence disease by altering gene expression in immune cells and minor salivary glands. Further, our analysis suggests that altered gene expression in the minor salivary gland expands beyond effects on the index gene to several genes on each locus. Interestingly, we observed minor salivary gland eQTLs for several BTN family genes, which act as cell-surface binding partners to regulate cell-cell interactions, including interactions between epithelial cells and activated T cells [3]. Future work will assess chromatin-chromatin-interactions within the 10 SjD risk loci in salivary gland cells and tissues to map local chromatin regulatory networks that regulate gene expression. Additional transcriptional studies of SjD minor salivary gland tissues will provide further insights into how altered gene expression in the salivary gland influences SjD pathology.References[1]Verstappen. Nat Rev Rheumatol 2021;17(6):333-348.[2]Khatri, et al. Annals of Rheumatic Diseases 2020;79:30-31.[3]Arnett HA, Viney JL. Nature Reviews Immunology 2014;14:559-569.Disclosure of InterestsFarhang Aghakhanian: None declared, Mandi M Wiley: None declared, Bhuwan Khatri: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen: None declared, Simon J. Bowman Consultant of: Abbvie, Galapagos, and Novartis in 2020-2021., Lida Radfar: None declared, Roald Omdal: None declared, Marie Wahren-Herlenius: None declared, Blake M Warner: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, Patrick M Gaffney: None declared, Judith A. James: None declared, Lars Ronnblom: None declared, R Hal Scofield: None declared, Xavier Mariette: None declared, Marta Alarcon-Riquelme: None declared, Wan Fai Ng: None declared, Kathy Sivils Employee of: Current employee of Janssen, Gunnel Nordmark: None declared, Umesh Deshmukh: None declared, A Darise Farris: None declared, Christopher Lessard: None declared
  •  
41.
  • Heitsch, L., et al. (author)
  • Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
  • 2021
  • In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:1, s. 132-141
  • Journal article (peer-reviewed)abstract
    • Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
  •  
42.
  •  
43.
  •  
44.
  • Khatri, B, et al. (author)
  • GENOME-WIDE ASSOCIATION STUDY OF SJOGREN'S SYNDROME IDENTIFIES TEN NEW RISK LOCI
  • 2020
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 30-31
  • Conference paper (other academic/artistic)abstract
    • Sjögren’s syndrome (SS) is a complex autoimmune disease with exocrine gland dysfunction leading to substantial morbidity. There are 10 published genetic susceptibility loci.Objectives:Our genome-wide association study (GWAS) aimed to identify additional risk loci of genome-wide significance (GWS; p<5E-08) in European-derived primary SS.Methods:A total of 3232 cases and 17481 controls genotyped on GWAS arrays and 619 cases and 6171 controls genotyped on ImmunoChip (IC) arrays were imputed after quality control. Logistic regression was calculated adjusting for ancestry using the first 4 principal components to identify SS-associated SNPs. GWAS and IC results were meta-analyzed using weighted Z-scores. Bayesian statistics were used to assign posterior probabilities and define credible SNP sets for each locus. Bioinformatic analyses were used to predict functionality.Results:Seven novel loci exceeded GWS in the GWAS analysis:NAB1,MIR146A-PTTG1,XKR6,MAPT-CRHR1,RPTOR-CHMP6-BAIAP2,TYK2andSYNGR1. Meta-analysis with IC data identified three more novel loci exceeding GWS:CD247,PRDM1-ATG5andTNFAIP3. Several additional loci with suggestive association (p<1E-05) were also identified:ADAMTSL2,CGNL1andPHRF1.Several identified loci have reported functional implications in immune regulation and autoimmune disease. In lupus, rs2431697 correlated with rs2431098, which was shown to alterMIR146Aexpression, resulting in type I interferon pathway imbalance. Similarly,TYK2risk association reportedly drives interferon, IL10 and RET signaling pathways.PRDM1encodes Blimp-1, a master regulator of immune cell differentiation.CD247encodes the zeta subunit of the T cell receptor complex.XKR6is implicated in apoptotic cell ingestion.ATG5is also involved in apoptosis, as well as autophagy and antigen presentation.Additional bioinformatics analyses (Haploreg, Regulome DB, ENCODE, etc.) revealed immune-relevant functional implications for each risk locus. The SS-associated credible set included variants downstream ofTNFAIP3in a region reported to abolish looping between an enhancer and theTNFAIP3promoter in lupus and a coding variant that has been shown to alter NF-kB activity and neutrophil extra-cellular traps. The rs2293765 in the 5’ UTR ofNAB1showed evidence of enhancer/promoter activities. The rs2069235 in theSYNGR1locus showed enhancer and transcription start site activities in B and T cells. The rs7210219 in theMAPT-CRHR1locus showed enhancer/promotor activities in various tissues.Conclusion:We have identified ten novel genetic susceptibility loci associated with SS pathology. Our finding increases the current number of GWS regions in SS patients of European origin, from 10 to 20. Future work is needed to identify and characterize the functional variants in each region.Disclosure of Interests:Bhuwan Khatri: None declared, Tove Ragna Reksten: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen Speakers bureau: Novartis, ThermoFischer, R Hal Scofield Grant/research support from: Pfizer, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Joel Guthridge Grant/research support from: Xencor, Bristol Myers Squibb, DXterity, Judith A. James Grant/research support from: Progentec Diagnostics, Inc, Consultant of: Abbvie, Novartis, Jannsen, Lars Ronnblom Grant/research support from: AZ, Speakers bureau: AZ, Blake M Warner: None declared, Xavier Mariette: None declared, Roald Omdal: None declared, Javier Martin Ibanez: None declared, Maria Teruel: None declared, Janicke Liaaen Jensen: None declared, Lara A Aqrawi: None declared, Øyvind Palm: None declared, Marie Wahren-Herlenius: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, A Darise Farris Speakers bureau: Biogen, Marta Alarcon-Riquelme: None declared, Wan-fai Ng: None declared, Kathy L Sivils: None declared, Gunnel Nordmark: None declared, Christopher Lessard: None declared
  •  
45.
  • Khatri, Sumita B., et al. (author)
  • Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline
  • 2021
  • In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 204:10, s. 97-109
  • Journal article (peer-reviewed)abstract
    • Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.
  •  
46.
  •  
47.
  •  
48.
  • Lamichhane, S., et al. (author)
  • First-Principles Study of Adsorption of Halogen Molecules on Graphene-MoS2 Bilayer Hetero-system
  • 2016
  • In: 24Th Condensed Matter Days National Conference (Cmdays2016). - : IOP Publishing.
  • Conference paper (peer-reviewed)abstract
    • We have performed density functional theory based first-principles calculations to study the stability, geometrical structures and electronic properties of pure 3x3 supercell of MoS2, 4x4 supercell of graphene, graphene-MoS2 bilayer hetero-system, F-2, Cl-2, Br-2 and I-2 molecules on hetero-system within the DFT-D-2 level of approximations. The preferable site and adsorption energy of halogen molecules are studied. The most stable geometries are considered to study their electronic band structure, Density of states and magnetic properties with reference to individual 2D components, graphene and MoS2.
  •  
49.
  •  
50.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 59

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view