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| 2. |
- Aglietta, M, et al.
(författare)
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The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
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Tidskriftsartikel (refereegranskat)abstract
- The cosmic ray primary composition in the energy range between 10(15) and 10(16) eV, i.e., around the "knee" of the primary spectrum, has been studied through the combined measurements of the EAS-TOP air shower array (2005 m a. s.l., 10(5) m(2) collecting area) and the MACRO underground detector (963 m.a.s.l., 3100 m w.e. of minimum rock overburden, 920 m(2) effective area) at the National Gran Sasso Laboratories. The used observables are the air shower size (N-c) measured by EAS-TOP and the muon number (N-mu) recorded by MACRO. The two detectors are separated on average by 1200 m of rock, and located at a respective zenith angle of about 30degrees. The energy threshold at the surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons are produced in the early stages of the shower development and in a kinematic region quite different from the one relevant for the usual N-mu - N-e studies. The measurement leads to a primary composition becoming heavier at the knee of the primary spectrum, the knee itself resulting from the steepening of the spectrum of a primary light component (p, He) of Deltay = 0.7 +/- 0.4 at E-0 similar to 4 x 10(15) eV. The result confirms the ones reported from the observation of the low energy muons at the surface (typically in the GeV energy range), showing that the conclusions do not depend on the production region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET) provides consistent composition results from data related to secondaries produced in a rapidity region exceeding the central one. Such an evolution of the composition in the knee region supports the "standard" galactic acceleration/propagation models that imply rigidity dependent breaks of the different components.. and therefore breaks occurring at lower energies in the spectra of the light nuclei. (C) 2003 Elsevier B.V. All rights reserved.
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| 3. |
- Aglietta, M, et al.
(författare)
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The cosmic ray proton, helium and CNO fluxes in the 100 TeV energy region from TeV muons and EAS atmospheric Cherenkov light observations of MACRO and EAS-TOP
- 2004
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
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Tidskriftsartikel (refereegranskat)abstract
- The primary cosmic ray (CR) proton, helium and CNO fluxes in the energy range 80-300 TeV are studied at the National Gran Sasso Laboratories by means of EAS-TOP (Campo Imperatore, 2005 m a.s.l.) and MACRO (deep underground, 3100 m w.e., the surface energy threshold for a muon reaching the detector being E-mu(th) approximate to 1.3 TeV). The measurement is based on: (a) the selection of primaries based on their energy/nucleon (i.e., with energy/nucleon sufficient to produce a muon with energy larger than 1.3 TeV) and the reconstruction of the shower geometry by means of the muons recorded by MACRO in the deep underground laboratories; (b) the detection of the associated atmospheric Cherenkov light (C.l.) signals by means of the C.l. detector of EAS-TOP. The C.l. density at core distance r > 100 m is directly related to the total primary energy E-0. Proton and helium ("p + He") and proton, helium and CNO ("p + He + CNO") primaries are thus selected at E-0 approximate to 80 TeV, and at E-0 similar or equal to 250 TeV, respectively. Their flux is measured: J(p+He)(80 TeV) = (1.8 +/- 0.4) x 10(-6) m(-1)-s(-1) sr(-1) TeV-1, and J(p+He+CNO)(250 TeV) = (1.1 +/- 0.3) x 10(-7) m(-2)-s(-1) sr(-1) TeV-1, their relative weights being J(p+He)(J(p+He+CNO)) over bar (250 TeV) = 0.78 +/- 0.17. By using the measurements of the proton spectrum obtained from the direct experiments and hadron flux data in the atmosphere, we obtain for the relative weights of the three components at 250 TeV: J(p) : J(He) : J(CNO) = (0.20 +/- 0.08) : (0.58 +/- 0.19) : (0.22 +/- 0.17). This corresponds to the dominance of helium over proton primaries at 100-1000 TeV, and a possible non-negligible contribution from CNO. The lateral distribution of Cherenkov light in Extensive Air Showers (EASs), which is related to the rate of energy deposit of the primary in the atmosphere, is measured for a selected proton and helium primary beam, and good agreement is found when compared with the one calculated with the CORSIKA/QGSJET simulation model. (C) 2004 Elsevier B.V. All rights reserved.
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| 7. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 9. |
- O’Reilly, Catherine M., et al.
(författare)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Tidskriftsartikel (refereegranskat)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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| 11. |
- Fanouriakis, Antonis, et al.
(författare)
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EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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| 12. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 13. |
- Maroni, F., et al.
(författare)
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Highly Stable Fe3O4/C Composite: A Candidate Material for All Solid-State Lithium-Ion Batteries
- 2020
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 1945-7111 .- 0013-4651. ; 167:7
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Tidskriftsartikel (refereegranskat)abstract
- Fe3O4 nanoparticles synthesized by a base catalyzed method are tested in an All-Solid-State (ASLB) battery using a sulfide electrolyte. The pristine nanoparticles were morphologically characterized showing an average size of 12 nm. The evaluation of the electrochemical properties shows high specific capacity values of 506 mAhg(-1) after 350 cycles at a specific current of 250 mAg(-1), with very high stability and coulombic efficiency. (C) 2020 The Author(s). Published on behalf of The Electrochemical Society by IOP Publishing Limited.
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| 14. |
- Sharma, Sapna, et al.
(författare)
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A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
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Ingår i: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
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| 15. |
- van Vollenhoven, R, et al.
(författare)
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A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:3, s. 554-561
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Tidskriftsartikel (refereegranskat)abstract
- Treat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
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| 18. |
- Werth, V, et al.
(författare)
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BIIB059, A HUMANIZED MONOCLONAL ANTIBODY TARGETING BDCA2 ON PLASMACYTOID DENDRITIC CELLS (PDC), SHOWS DOSE-RELATED EFFICACY IN THE PHASE 2 LILAC STUDY IN PATIENTS (PTS) WITH ACTIVE CUTANEOUS LUPUS ERYTHEMATOSUS (CLE)
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 120-121
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- CLE represents an unmet medical need with no approved therapy. BIIB059, a humanized monoclonal antibody, binds to BDCA2 and inhibits pro-inflammatory mediators production, including type I interferons. BIIB059 was evaluated in Phase 1 studiesNCT02106897andNCT03224793. LILAC is a 2-part Phase 2 study: Part A enrolled SLE pts; Part B enrolled pts with active CLE (NCT02847598).Objectives:Evaluate efficacy and safety of BIIB059 in pts enrolled in Part B at Week 16, end of treatment (EOT) period.Methods:Pts with active CLE, SCLE and/or CCLE and adjudicated Cutaneous Lupus Disease Area and Severity Index – Activity (CLASI-A) ≥8 were enrolled and randomized to receive either BIIB059 (50, 150 or 450 mg) or placebo (PBO) s.c. Q4W. Primary endpoint was dose response defined by % change in CLASI-A score from baseline (BL) to Week 16. Secondary endpoints included CLASI-50 response rate and ≥ 7-point reduction in CLASI-A score from baseline to EOT. Adverse events and serious adverse events were recorded throughout the study.Results:132 pts with active CLE were randomized. The study met its primary endpoint, demonstrating a dose response (p= 0.0005) and a statistically significant difference in % change from BL in CLASI-A score in BIIB059-treated pts vs PBO. Table 1 and Table 2 summarize efficacy and safety results, respectively.Table 1.Efficacy EndpointsBIIB059PBO50 mg150 mg450 mgLS Mean (SE)LS Mean (SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.Primary EndpointCLASI-A % change from BL-14.5 (6.4)-40.8 (7.5)-26.3 (-45.7; -7.0)0.008-47.9 (7.4)-33.5 (-52.7; -14.3)0.001-43.5 (5.5)-28.0 (-44.5; -11.5)0.001Secondary Endpointsn(%)n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.Prop. of participants achieving CLASI 507/32 (21.9%)10/26 (38.5%)15.8% (-7; 39)0.13311/25 (44.0%)21 (-2.8; 45)0.05920/43 (46.5%)23 (3; 44)0.024Prop. of participants achieving a ≥7-point CLASI-A reduction from BL7/32 (21.9%)9/26 (34.6%)12.3 (-11.3; 35.8)0.22812/25 (48.0%)22.2 (-2.0; 46.3)0.05518/43 (41.8%)16.8 (-6.7; 40.4)0.048*LSMD=LS Mean DifferencePBOBIIB059OVERALLN=3350 mgN=26150 mgN=25450 mgN=48PooledN=99N=132Any Event, n(%)18 (54.5)17 (65.4)12 (48)33 (68.8)62 (62.6)80 (60.6)SeverityMild11 (33.3)11 (42.3)8 (32.0)19 (39.6)38 (38.4)49 (37.1)Moderate4 (12.1)6 (23.1)3 (12.0)12 (25.0)21 (21.2)25 (18.9)Severe3 (9.1)01 (4.0)2 (4.2)3 (3.0)6 (4.5)Related events6 (18.2)9 (34.6)4 (16.0)16 (33.3)29 (29.3)35 (26.5)Serious events2 (6.1)03 (12.0)2 (4.2)5 (5.1)7 (5.3)Related serious events1 (3.0)01 (4.0)1 (2.1)2 (2.0)3 (2.3)Events leading to drug withdrawal01 (3.8)1 (4.0)1 (2.1)3 (3.0)3 (2.3)Events leading to study withdrawal0001 (2.1)1 (1.0)1 (0.8)Fatal events000000Conclusion:BIIB059 administration to pts with active CLE resulted in statistically significant dose-related improvement in disease activity vs PBO with no untoward safety signals. Further development of BIIB059 in CLE is warranted.Disclosure of Interests:Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Juanita Romero-Diaz Consultant of: Biogen, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Filippa Nyberg Consultant of: Biogen, Benjamin Kaffenberger Grant/research support from: Amgen, Biogen, InflaRx, Veloce Biopharmaceuticals, Dermatology Foundation, Saira Sheikh: None declared, Goran Radunovic: None declared, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Francois Gaudreault Shareholder of: Biogen, Employee of: Biogen, Adam Meyers Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, Employee of: Biogen
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