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- Fredholm, BB, et al.
(författare)
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Consequences of eliminating adenosine A(1) receptors in mice
- 2003
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Ingår i: Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1). - : Wiley. - 1098-2299 .- 0272-4391. ; 58, s. 350-
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Konferensbidrag (refereegranskat)abstract
- The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
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- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)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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- Ax, AK, et al.
(författare)
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Cost effectiveness of high versus low-to-moderate intensity exercise during oncological treatment : The Phys-Can RCT
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534.
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Konferensbidrag (refereegranskat)abstract
- Background A cost-effectiveness analysis, considering both costs and health outcomes of interventions, are important for decision-making and implementation in the health care. Exercise during oncological treatment is beneficial for health and have been found to counteract side effects of treatment. The Swedish Phys-Can RCT compared a six-month exercise program combining supervised resistance training and homebased endurance training of high-intensity (HI) versus low-to-moderate intensity (LMI), with or without additional behaviour change support. At post intervention, HI yielded small improvements of fitness and physical fatigue compared with LMI. At 18 months, no differences were found in total costs between the intensities. However, knowledge of the cost effectiveness in exercise interventions with regard to intensity is limited. In this study, we aimed to evaluate the long-term cost-effectiveness of an exercise program at HI versus LMI during oncological treatment. Methods A cost-effectiveness analysis was undertaken from a societal perspective for 18 months. 189 (n=99 HI and n=90 LMI) participants with breast, colorectal, or prostate cancer were included from the Phys-Can RCT. Health outcomes were measured as quality-adjusted life years (QALYs), using EQ-5D-5L at baseline, six months and 18 months. Costs included the exercise intervention, health care utilisation and productivity loss. Results At 18 months, the total cost per participant did not differ significantly between HI (€27,314) and LMI exercise (€29,788). There was no significant difference in health outcome between the intensities. On average HI generated 1.190 (SD = 0.223) QALYs and LMI 1.185 (SD = 0.211) QALYs for 18 months, meaning HI led to an additional 0.005 QALYs. The incremental cost-effectiveness ratio (ICER) indicates that HI was more effective and saved costs compared with LMI. Conclusions The uncertainty around the ICER was large, however our results indicates that HI exercise was cost-effective compared to LMI exercise at longer term since there was lower total costs per QALY gained. Thus, we suggest that exercise with its health benefits may be implemented regardless of intensity.
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