| 1. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 2. |
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| 3. |
- Gilbert, M. Thomas P., et al.
(författare)
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Paleo-Eskimo mtDNA genome reveals matrilineal discontinuity in Greenland
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 320:5884, s. 1787-1789
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Tidskriftsartikel (refereegranskat)abstract
- The Paleo- Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New World's northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo- Eskimo human by using 3400- to 4500- year- old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo- Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New World's northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo- Eskimos that replaced them.
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| 4. |
- Möller, Niels, et al.
(författare)
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Modeling and control of IP transport in cellular radio links
- 2005
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Konferensbidrag (refereegranskat)abstract
- A fundamental assumption of the TCP protocol is that packet losses indicate congestion on the network. This is a problem when using TCP over wireless links, because a noisy radio transmission may erroneously indicate congestion and thereby reduce the TCP sending rate. Two partial solutions, which improve the quality of the radio link, are power control and link-layer retransmissions. We consider a radio channel with multiple users and traffic classes, and investigate how parameters in the radio model influences TCP-related quality measures, such as the average delay and the probability of spurious timeout. The results indicate that the outer loop power control is robust to uncertainties in the radio model. This robustness property supports separation between the radio layer design and the IP and TCP layers.
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| 5. |
- Möller, N., et al.
(författare)
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Modelling and control of IP transport in cellular radio links
- 2005
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Konferensbidrag (refereegranskat)abstract
- A fundamental assumption of the TCP protocol is that packet losses indicate congestion on the network. This is a problem when using TCP over wireless links, because a noisy radio transmission may erroneously indicate congestion and thereby reduce the TCP sending rate. Two partial solutions, which improve the quality of the radio link, are power control and link-layer retransmissions. We consider a radio channel with multiple users and traffic classes, and investigate how parameters in the radio model influences TCP-related quality measures, such as the average delay and the probability of spurious timeout. The results indicate that the outer loop power control is robust to uncertainties in the radio model. This robustness property supports separation between the radio layer design and the ip and TCP layers.
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| 6. |
- Baruch, Lawrence, et al.
(författare)
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Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified?
- 2007
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 38:9, s. 2459-2463
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Patients with atrial fibrillation have a varied risk of stroke, depending on age and comorbid conditions. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation who are at substantial risk of stroke despite optimal anticoagulant therapy. Methods - Seven recognized classification schemes - the American College of Chest Physicians 2001, American College of Chest Physicians 2004, Stroke Prevention in Atrial Fibrillation (SPAF), Atrial Fibrillation Investigators, Framingham, van Walraven, and CHADS(2) - were compared for their ability to predict ischemic stroke in patients receiving anticoagulant therapy. Data came from the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials, which compared the efficacy of adjusted-dose warfarin and the direct thrombin inhibitor ximelagatran (36 mg twice daily) in preventing thromboembolic events in 7329 patients with chronic or paroxysmal nonvalvular atrial fibrillation who were at moderate or high risk of ischemic stroke. The main outcome measure was ischemic stroke, as determined by a central event adjudication committee. Results - During 11 245 patient-years of follow-up, 159 patients had an ischemic stroke (1.4%/year). As indicated by c statistics and hazard ratios, 3 of the classification schemes predicted stroke significantly better than chance: Framingham (c = 0.64), CHADS2 (c = 0.65), and SPAF (c = 0.61). Conclusions - In a large cohort of atrial fibrillation patients at moderate or high risk of ischemic stroke treated with warfarin or ximelagatran, the CHADS2, SPAF, and Framingham schemes had greater predictive accuracy than chance. This predictive ability may allow clinicians to target high-risk patients for more aggressive intervention.
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| 7. |
- Bayer, Daniel, et al.
(författare)
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Dynamic Runtime Environments for Grid Computing
- 2008
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Ingår i: CGW'07 Proceedings. - 9788391514191 ; , s. 155-162
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Konferensbidrag (refereegranskat)abstract
- In a grid computing context the execution of jobs on remote machines of collaborating institutes often requires the provisioning of more than mere CPU time. Besides libraries and utilities distributed with the operating system in question, further software may be required by the jobs and in such cases need to be installed prior to the job's execution. In grid computing this problem is aggravated by decreased personal contacts among collaborators. Currently, Virtual Organisations of existing production grids typically agree on a set of runtime environments that participating sites install manually. The challenge is to automate this process, thus easing the burden of the site's maintainers and allowing grid-wide software updates with immediate eject. This paper presents an RDF based schema for the description of runtime environments and the implementation of a service for their automated and dynamic installation.
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| 8. |
- Di Marco, P., et al.
(författare)
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Performance analysis and optimization of TCP over adaptive wireless links
- 2006
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Ingår i: Personal, Indoor and Mobile Radio Communications, 2006 IEEE 17th International Symposium on <em> </em>. - : IEEE. - 1424403294 ; , s. 1-6
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Konferensbidrag (refereegranskat)abstract
- This paper proposes an analytical framework for performance evaluation of TCP (transport control protocol) over adaptive wireless links. Specifically, we include adaptation of power, modulation format and error recovery strategy, and incorporate some features of wireless fading channels. This framework is then used to pursue joint optimization through maximization of an objective functional, that expresses a trade-off between achievable throughput and energy costs. A set of numerical results is reported, and it is seen that hybrid ARQ schemes may provide significant benefits in the optimization framework.
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| 9. |
- Ekqvist, Susanne, et al.
(författare)
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Does gold concentration in the blood influence the result of patch testing to gold?
- 2009
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 160:5, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B-Au) in a stented population: the higher the B-Au, the stronger the patch-test reaction. To further investigate the correlation between B-Au and patch-test reactivity to gold. In this provocation control cross-over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1.1 mg GSTS). Patch-test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa. B-Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B-Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B-Au and/or booster effect from test occasion I. There was a correlation between B-Au and MEC: the higher the B-Au, the lower the MEC. The correlation between B-Au and MEC indicates that the B-Au is of importance for the skin reactivity to gold.
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| 10. |
- Fischer, Marie, et al.
(författare)
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Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion
- 2006
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 116:10, s. 2748-2756
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.
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| 11. |
- Gatta, G, et al.
(författare)
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Survival from rare cancer in adults: a population-based study
- 2006
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Ingår i: The Lancet Oncology. - 1474-5488. ; 7:2, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Background Rare cancers are a challenge to clinical practice, and treatment experience, even in major cancer centres to which rare cancers are usually referred, is often limited. We aimed to study the epidemiology of rare cancers in a large population of several countries. Methods We analysed survival by age, sex, subsite, and morphology in 57 144 adults with 14 selected rare cancers diagnosed 1983-94. Variations in survival over time and between European regions were also assessed for variations in quality of care. We also estimated the adjusted relative excess risk of death for every rare cancer. Findings Overall 5-year relative survival was good (ie, > 65%) for placental choriocarcinoma (85-4% [95% CI 81.4-89.5]), thyroid medullary carcinoma (72.4% [69.2-75.5]), ovarian germ-cell cancer (73.0% [70.0-76.0]), lung carcinoid (70.1% [67.3-72.9]), and cervical adenocarcinoma (65.5% [64.3-66.6]); intermediate (ie, 35-65%) for testicular cancer at age 65 years or older (64.0% [59.3-68.7]), sarcoma of extremities (60.0% [58.9-61.2]), digestive-system endocrine cancers (55.6% [54.9-56.3]), anal squamous-cell carcinoma (53.1% [51.5-54.8]), and uterine sarcoma (43.5% [42.0-44.9]); low for carcinoma of adrenal-gland cortex (32-7% [28.3-37.2]) and bladder squamous-cell carcinoma (20.4% [18.8-22.0]); and poor for angiosarcoma of liver (6-4% [1.8-11.0]) and mesothelioma (4.7% [4.3-5.2]). Survival was usually better for women than men and poor in those aged 75 years or older. Survival significantly improved over time for ovarian germ-cell cancer, sarcomas of extremities, digestive-system endocrine tumours, anal squamous-cell carcinoma, and angiosarcoma of liver. Survival in northern Europe was higher than in the other geographic groupings for most cancers. Interpretation Because effective treatments are available for several of the rare cancers we assessed, further research is needed to ascertain why survival is lower in some European countries than in others, particularly in older patients. Audit of best practice for rare cancers with treatment protocols would be useful.
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| 12. |
- Gustafsson, Johanna, et al.
(författare)
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Predictors of the first cardiovascular event in patients with systemic lupus erythematosus : a prospective cohort study
- 2009
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:6, s. R186-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION :Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.METHODS : A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.RESULTS :Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.CONCLUSIONS : In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.
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| 14. |
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| 15. |
- Stracke, C P, et al.
(författare)
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Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T.
- 2005
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 47:2, s. 127-33
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans.
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