| 1. |
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| 2. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 3. |
- Algaba, Juan-Carlos, et al.
(author)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 9. |
- Niemi, MEK, et al.
(author)
-
- 2021
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swepub:Mat__t
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| 10. |
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| 11. |
- Adcox, K, et al.
(author)
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Centrality dependence of the high (PT) charged hadron suppression in Au+Au collisions at root s(NN)=130 GeV
- 2003
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 561:1-2, s. 82-92
-
Journal article (peer-reviewed)abstract
- PHENIX has measured the centrality dependence of charged hadron p(T) spectra from Au +An collisions at root(s)NN = 130 GeV The truncated mean p(T) decreases with centrality for p(T) > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p(T) hadrdn production. For central collisions the yield at high p(T) is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p + p, data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e., for collisions with less than similar to140 participating nucleons. The observed p(T) and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions. (C) 2003 Published by Elsevier Science B.V.
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| 12. |
- Adcox, K, et al.
(author)
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Event-by-event fluctuations in mean p(T) and mean E(T) in root s(NN)=130 GeVAu+Au collisions
- 2002
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:2
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Journal article (peer-reviewed)abstract
- Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at roots(NN)=130 GeV at the Relativistic Heavy-Ion Collider. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of nonstatistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant nonrandom fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p(T) or e(T) spectra, we exclude a region of fluctuations in roots(NN)=130 GeV Au+Au collisions.
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| 13. |
- Adcox, K, et al.
(author)
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Flow Measurements via Two-Particle Azimuthal Correlations in Au+Au Collisions at sqrt[sNN]=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 89
-
Journal article (peer-reviewed)abstract
- Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider (sqrt[sNN]=130 GeV). The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values (v2) show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone ε, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low pT. A breakdown of this ε scaling is observed for charged hadrons with pT >1.0 GeV/c.
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| 14. |
- Adcox, K, et al.
(author)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Research review (peer-reviewed)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 15. |
- Adcox, K, et al.
(author)
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Measurement of Lambda and (Lambda)over-bar particles in Au plus Au collisions at root s(NN)=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 89:9
-
Journal article (peer-reviewed)abstract
- We present results on the measurement of Lambda and (&ULambda;) over bar production in Au+Au collisions at roots(NN)=130 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider. The transverse momentum spectra were measured for minimum bias and for the 5% most central events. The (&ULambda;) over bar/Lambda ratios are constant as a function of p(T) and the number of participants. The measured net Lambda density is significantly larger than predicted by models based on hadronic strings (e.g., HIJING) but in approximate agreement with models which include the gluon-junction mechanism.
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| 16. |
- Adcox, K, et al.
(author)
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Measurement of single electrons and implications for charm production in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 88:19
-
Journal article (peer-reviewed)abstract
- Transverse momentum spectra of electrons from Au+Au collisions at roots(NN) = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025 +/- 0.004(stat) +/- 0.010( syst) in central collisions, and the corresponding charm cross section is 380 +/- 60(stat) +/- 200(syst ) mub per binary nucleon-nucleon collision.
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| 17. |
- Adcox, K, et al.
(author)
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Net charge fluctuations in Au+Au interactions root s(NN)=130 GeV
- 2002
-
In: Physical Review Letters. - 1079-7114. ; 89
-
Journal article (peer-reviewed)abstract
- Data from Au+ Au interactions at s(NN)=130 GeV, obtained with the PHENIX detector at the Relativistic Heavy-Ion Collider, are used to investigate local net charge fluctuations among particles produced near midrapidity. According to recent suggestions, such fluctuations may carry information from the quark-gluon plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.
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| 18. |
- Adcox, K, et al.
(author)
-
PHENIX detector overview
- 2003
-
In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
-
Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 19. |
- Adcox, K, et al.
(author)
-
Suppression of hadrons with large transverse momentum in central Au+Au collisions at root s(NN)=130 GeV
- 2002
-
In: Physical Review Letters. - 1079-7114. ; 88:2
-
Journal article (peer-reviewed)abstract
- Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 Gev/c < P-T < 5 GeV/c have been measured by the PHENIX experiment at RHIC in Au + Au collisions at rootS(NN) = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p + p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p + p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.
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| 20. |
- Adcox, K, et al.
(author)
-
Transverse-mass dependence of two-pion correlations in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
-
In: Physical Review Letters. - 1079-7114. ; 88:19
-
Journal article (peer-reviewed)abstract
- Two-pion correlations in roots(NN) = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to results from heavy-ion collisions at roots(NN) = 4.1 , 4.9, and 17.3 GeV, whereas the longitudinal radius increases monotonically with beam energy. The ratio of the outwards to sidewards transverse radii (R-out/R-side) is consistent with unity and independent of k(T) .
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Ashton, Susan, et al.
(author)
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Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo
- 2016
-
In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:325
-
Journal article (peer-reviewed)abstract
- Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.
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| 26. |
- Brune, Mats, 1950, et al.
(author)
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Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial
- 2006
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:1, s. 88-96
-
Journal article (peer-reviewed)abstract
- The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.
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| 27. |
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| 28. |
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| 29. |
- Chu, Tak-Ho, et al.
(author)
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Axonal and myelinic pathology in 5xFAD Alzheimers mouse spinal cord
- 2017
-
In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:11
-
Journal article (peer-reviewed)abstract
- As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimers research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimers mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimers pathology and disease progression.
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| 30. |
- Dahlgren, Jovanna, 1964, et al.
(author)
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Prenatal cytokine exposure results in obesity and gender-specific programming.
- 2001
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In: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 281:2
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Journal article (peer-reviewed)abstract
- Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.
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| 31. |
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| 33. |
- Heckman, Michael G., et al.
(author)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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In: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Journal article (peer-reviewed)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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| 34. |
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| 35. |
- Ho, Hoi-Por, 1962, et al.
(author)
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Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women.
- 2004
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 58:2, s. 109-110
-
Journal article (peer-reviewed)abstract
- Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.
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| 36. |
- Kaptoge, S., et al.
(author)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
-
Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 37. |
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| 38. |
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| 39. |
- Lacas, Benjamin, et al.
(author)
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Role of radiotherapy fractionation in head and neck cancers (MARCH) : an updated meta-analysis
- 2017
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:9, s. 1221-1237
-
Journal article (peer-reviewed)abstract
- Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Funding Institut National du Cancer; and Ligue Nationale Contre le Cancer.
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| 40. |
- LAGERHOF, HO, et al.
(author)
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ISIS-4
- 1995
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In: Lancet (London, England). - 0140-6736. ; 345:8961, s. 1372-1372
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Journal article (other academic/artistic)
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| 41. |
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| 42. |
- Michaëlsson, Karl, 1959-, et al.
(author)
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Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates
- 1996
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 25:2, s. 403-10
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Journal article (peer-reviewed)abstract
- BACKGROUND. Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. METHODS. More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. RESULTS. The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. CONCLUSION. We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.
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| 45. |
- Nilsson, Cecilia, et al.
(author)
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Increased insulin sensitivity and decreased body weight in female rats after postnatal corticosterone exposure.
- 2002
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 146:6, s. 847-54
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Glucocorticoids are important for normal brain development. Elevation or removal of these hormones can permanently modify the structure and function of the fetal brain. The purpose of this study was to examine the effects of postnatal corticosterone exposure of female pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of corticosterone (5 mg/kg, CORT) or vehicle 3 and 5 days after birth. RESULTS: From 6 weeks of age, the CORT rats weighed significantly less than did controls, with diminished fat depots, decreased serum levels of leptin and reduced food intake. Adult CORT rats showed increased insulin sensitivity, measured by hyperinsulinemic, euglycemic clamp (5 mU/kg/min), as compared with controls. CORT rats had lower basal corticosterone levels and lower corticosterone levels 15 and 90 min after exposure to stress. CONCLUSION: The results indicate that postnatal exposure to corticosterone leads to increased insulin sensitivity, low body weight with diminished fat depots, leptin and food intake. This suggests that postnatal exposure to corticosterone induces specific programming, with consequences in adult life.
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| 46. |
- Nilsson, Cecilia, et al.
(author)
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Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.
- 2002
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 146:2, s. 251-60
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. RESULTS: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) and testosterone tended to be higher. CONCLUSION: The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.
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| 47. |
- Nilsson, Cecilia, et al.
(author)
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Reductions in adipose tissue and skeletal growth in rat adult offspring after prenatal leptin exposure.
- 2003
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In: The Journal of endocrinology. - 0022-0795. ; 176:1, s. 13-21
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Journal article (peer-reviewed)abstract
- Leptin is involved in regulating food intake, energy balance and bone formation. Increasing evidence suggests that leptin is also involved in fetal growth and development. The aim of this study was to determine if increased maternal leptin is followed by changes in body composition, skeletal growth or hormonal regulation in the adult rat offspring. Pregnant rats were given injections of either human recombinant leptin (3.5 mg/kg, i.p.) or vehicle on days 8, 10 and 12 of gestation. Both genders of leptin-exposed offspring showed significantly reduced adipose tIssue weight at adult age. Skeletal growth and cortical bone dimensions were significantly reduced. Circulating testosterone levels were significantly increased in female leptin-exposed offspring, and male leptin-exposed offspring had significant testicular enlargement. No significant effects were seen on circulating leptin levels or hypothalamic protein levels of the leptin receptor. The results demonstrate that maternally administered leptin is involved in fetal growth and development, leading to lean offspring with reduced skeletal growth.
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| 48. |
- Ning, Yilin, et al.
(author)
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Handling ties in continuous outcomes for confounder adjustment with rank-ordered logit and its application to ordinal outcomes
- 2020
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In: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 29:2, s. 437-454
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Journal article (peer-reviewed)abstract
- The rank-ordered logit (rologit) model was recently introduced as a robust approach for analysing continuous outcomes, with the linear exposure effect estimated by scaling the rank-based log-odds estimate. Here we extend the application of the rologit model to continuous outcomes with ties and ordinal outcomes treated as imperfectly-observed continuous outcomes. By identifying the functional relationship between survival times and continuous outcomes, we explicitly establish the equivalence between the rologit and Cox models to justify the use of the Breslow, Efron and perturbation methods in the analysis of continuous outcomes with ties. Using simulation, we found all three methods perform well with few ties. Although an increasing extent of ties increased the bias of the log-odds and linear effect estimates and resulted in reduced power, which was somewhat worse when the model was mis-specified, the perturbation method maintained a type I error around 5%, while the Efron method became conservative with heavy ties but outperformed Breslow. In general, the perturbation method had the highest power, followed by the Efron and then the Breslow method. We applied our approach to three real-life datasets, demonstrating a seamless analytical workflow that uses stratification for confounder adjustment in studies of continuous and ordinal outcomes.
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| 49. |
- Orsini, S., et al.
(author)
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Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission
- 2022
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Mercury’s southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury’s magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.
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