| 1. |
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| 2. |
- Emile-Geay, J., et al.
(author)
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Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era
- 2017
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Journal article (peer-reviewed)abstract
- Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike.
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| 3. |
- Smerdon, J. E., et al.
(author)
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Comparing proxy and model estimates of hydroclimate variability and change over the Common Era
- 2017
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 13:12, s. 1851-1900
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Journal article (peer-reviewed)abstract
- Water availability is fundamental to societies and ecosystems, but our understanding of variations in hydroclimate (including extreme events, flooding, and decadal periods of drought) is limited because of a paucity of modern instrumental observations that are distributed unevenly across the globe and only span parts of the 20th and 21st centuries. Such data coverage is insufficient for characterizing hydroclimate and its associated dynamics because of its multidecadal to centennial variability and highly regionalized spatial signature. High-resolution (seasonal to decadal) hydroclimatic proxies that span all or parts of the Common Era (CE) and paleoclimate simulations from climate models are therefore important tools for augmenting our understanding of hydroclimate variability. In particular, the comparison of the two sources of information is critical for addressing the uncertainties and limitations of both while enriching each of their interpretations. We review the principal proxy data available for hydroclimatic reconstructions over the CE and highlight the contemporary understanding of how these proxies are interpreted as hydroclimate indicators. We also review the available last-millennium simulations from fully coupled climate models and discuss several outstanding challenges associated with simulating hydroclimate variability and change over the CE. A specific review of simulated hydroclimatic changes forced by volcanic events is provided, as is a discussion of expected improvements in estimated radiative forcings, models, and their implementation in the future. Our review of hydroclimatic proxies and last-millennium model simulations is used as the basis for articulating a variety of considerations and best practices for how to perform proxy-model comparisons of CE hydroclimate. This discussion provides a framework for how best to evaluate hydroclimate variability and its associated dynamics using these comparisons and how they can better inform interpretations of both proxy data and model simulations. We subsequently explore means of using proxy-model comparisons to better constrain and characterize future hydroclimate risks. This is explored specifically in the context of several examples that demonstrate how proxy-model comparisons can be used to quantitatively constrain future hydroclimatic risks as estimated from climate model projections.
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| 4. |
- Mesas-Burgos, C, et al.
(author)
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Lung morphology after late fetal tracheal ligation in rats
- 2006
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In: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. - : Georg Thieme Verlag KG. - 0939-7248. ; 16:3, s. 160-165
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Journal article (peer-reviewed)
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| 5. |
- Ahlm, Clas, 1956-, et al.
(author)
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Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)
- 1998
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In: Journal of Infection. - 0163-4453 .- 1532-2742. ; 36:2, s. 149-155
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Journal article (peer-reviewed)abstract
- Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.
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| 6. |
- Almlen, A, et al.
(author)
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Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome
- 2008
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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 104:4, s. 1101-1108
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Journal article (peer-reviewed)abstract
- Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of ∼5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.
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| 7. |
- Andersson, J, et al.
(author)
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A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin (R)) on a named patient basis in Sweden
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 276-281
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Journal article (peer-reviewed)abstract
- Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p=0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.
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| 8. |
- Buntgen, U., et al.
(author)
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Tree rings reveal globally coherent signature of cosmogenic radiocarbon events in 774 and 993 CE
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the 14C content in 484 individual tree rings formed in the periods 770–780 and 990–1000 CE. Distinct 14C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved 14C measurements are needed.
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| 9. |
- Calkovska, A, et al.
(author)
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Biophysical and physiological properties of porcine surfactant enriched with polymyxin B
- 2005
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In: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 88:2, s. 101-108
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Journal article (peer-reviewed)abstract
- <i>Objective:</i> We examined whether the biophysical and physiological properties of Curosurf<sup>®</sup> were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). <i>Methods:</i> Curosurf was diluted to 1–5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (γ<sub>min</sub>) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. <i>Results:</i> At surfactant concentration 2 mg/ml, γ<sub>min</sub> was high (17 ± 8.9 mN/m) but remained low (2.7 ± 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. <i>Conclusion:</i> Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.
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| 10. |
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| 11. |
- Calkovska, A, et al.
(author)
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Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits
- 2016
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In: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 109:3, s. 177-185
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. <b><i>Objectives:</i></b> To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. <b><i>Methods:</i></b> Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. <b><i>Results:</i></b> Treatment with Curosurf® or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (V<sub>T</sub>) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small V<sub>T</sub>, but after addition of both analogues V<sub>T</sub> was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-<i>sn</i>-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on V<sub>T</sub> and LGV as Curosurf. <b><i>Conclusions:</i></b> Phospholipid composition is important for V<sub>T</sub> while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding V<sub>T</sub> and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Cook, ER, et al.
(author)
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Old World megadroughts and pluvials during the Common Era
- 2015
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 1:10
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Journal article (peer-reviewed)abstract
- Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. TheOWDAmatches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability.
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| 16. |
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| 17. |
- Eiermann, W, et al.
(author)
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Triple negative breast cancer: Proposals for a pragmatic definition and implications for patient management and trial design.
- 2012
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In: Breast. - : Elsevier BV. - 1532-3080. ; 21:1, s. 20-6
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Journal article (peer-reviewed)abstract
- In trials in triple negative breast cancer (TNBC), oestrogen and progesterone receptor negativity should be defined as<1% positive cells. Negativity is a ratio of <2 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less. In routine practice, immunohistochemistry is acceptable given stringent quality assurance. Triple negativity emerging after neoadjuvant treatment differs from primary TN and such patients should not enter TNBC trials. Patients relapsing with TN metastases should be eligible even if their primary was positive. Rare TN subtypes such as apocrine, adenoid-cystic and low-grade metaplastic tumours should be excluded. TN and basal-like (BL) signatures overlap but are not equivalent. Since the significance of basal cytokeratin or EGFR overexpression is not known and we lack validated assays, these features should not be used to subclassify TN tumours. Tissue collection in trials is mandatory so the effect on outcome of different tumour phenotypes and BRCA mutation can be explored. No prospective studies have established that TN tumours have particular sensitivity or resistance to any specific chemotherapy agent or radiation. TNBC patients should be treated according to tumour and clinical characteristics.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Linderholm, B. K., et al.
(author)
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Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel
- 2013
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In: Breast. - : Elsevier BV. - 1532-3080. ; 22:6, s. 1142-1147
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Journal article (peer-reviewed)abstract
- Background: Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. Aims: To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. Material and methods: Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. Results: Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease >= 24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). Conclusions: The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy. (C) 2013 Elsevier Ltd. All rights reserved.
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| 23. |
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| 24. |
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| 25. |
- Liu, Jiandong, et al.
(author)
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Changes in the relationship between solar radiation and sunshine duration in large cities of China
- 2015
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In: Energy. - : Elsevier BV. - 0360-5442. ; 82, s. 589-600
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Journal article (peer-reviewed)abstract
- Based on the linear relationship between solar radiation and sunshine duration, the Angstrom model is widely used to estimate solar radiation from routinely observed meteorological variables for energy exploitation. However, the relationship may have changed in quickly developing regions in the recent decades under global "dimming" and "brightening" context, with increasing aerosols due to industrial pollutions. Solar radiation stations under different climate conditions in six large cities in China are selected to test this hypothesis. Analysis of the related meteorological items shows that Guiyang has the lowest solar radiation with the average annual value of 10.5 MJm(-2)d(-1), while Lhasa on the Tibetan Plateau has the highest of 20.1 MJm(-2)d(-1). Both radiation and sunshine hours decreased from 1961 to 2010, but at different rates. A moving linear regression method is used to investigate the changes in the relationship between radiation and sunshine duration, the results indicate an abrupt change in the correlation coefficients in 1980-1990s, which can be attributed to the aerosol load resulting from air pollution caused by the industrial development in 1980s under China's Open Door Policy. The sky condition has been changing from clean to dirty, thus the relationship between solar radiation and duration changes in the 1980's and has recovered in the recent decades. This finding implies that it might not necessarily be right to use long data sets for model calibration. Further investigation confirms that the Angstrom model performs the best with higher NSE (nash-sutcliffe efficiency) of 0.914 and lower MAPE (mean absolute percentage error) and RMSE (root mean square error) values of 13.7 w/m(2) and 23.9 w/m(2) respectively, when calibrated with a 10-year data set. In contrast, the model performs worst when it is calibrated with a 40-year data set, with NSE, MAPE and RMSE values of 0.891, 15.1 w/m(2) and 25.3 w/m(2), respectively. Based on the findings of this research, a 10-year data set is recommended as the national standard for model calibration in rapidly developing regions of China. Further analogous investigations are needed in other industrial regions to make an international standard for Angstrom model calibration. (C) 2015 Elsevier Ltd. All rights reserved.
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| 26. |
- Liu, Y., et al.
(author)
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Anthropogenic Aerosols Cause Recent Pronounced Weakening of Asian Summer Monsoon Relative to Last Four Centuries
- 2019
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 46:10, s. 5469-5479
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Journal article (peer-reviewed)abstract
- The Asian Summer Monsoon (ASM) affects ecosystems, biodiversity, and food security of billions of people. In recent decades, ASM strength (as represented by precipitation) has been decreasing, but instrumental measurements span only a short period of time. The initiation and the dynamics of the recent trend are unclear. Here for the first time, we use an ensemble of 10 tree ring-width chronologies from the west-central margin of ASM to reconstruct detail of ASM variability back to 1566 CE. The reconstruction captures weak/strong ASM events and also reflects major locust plagues. Notably, we found an unprecedented 80-year trend of decreasing ASM strength within the context of the 448-year reconstruction, which is contrary to what is expected from greenhouse warming. Our coupled climate model shows that increasing anthropogenic sulfate aerosol emissions over the Northern Hemisphere could be the dominant factor contributing to the ASM decrease. Plan Language Summary Monsoonal rainfall has a certain influence on agriculture and industry in the regions of Asian Summer Monsoon (ASM). An understanding of the spatial-temporal variability of the ASM and the associated dynamics is vital for terrestrial ecosystems, water resources, forests, and landscapes. We have developed a 448-year ASM reconstruction back to 1566 CE using 10 tree ring chronologies from the margin region of ASM. We find that historical severe droughts and locust plague disasters during weak ASM events. The recent decreasing ASM trend persisting for over 80 years is unprecedented over the past 448 years. Coupled climate models show that increasing anthropogenic aerosol emissions are the dominant underlying factor. Our aim is that the time series will find a wide range of utility for understanding past climate variability and for predicting future climate change.
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| 27. |
- Liu, Y., et al.
(author)
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Recent enhancement of central Pacific El Nino variability relative to last eight centuries
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The far-reaching impacts of central Pacific El Nino events on global climate differ appreciably from those associated with eastern Pacific El Nino events. Central Pacific El Nino events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NINO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Nino4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Nino-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
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| 28. |
- Loman, N., et al.
(author)
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Nordic trip, a randomized phase 3 study in early triple negative breast cancer
- 2016
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In: Cancer Research. - Lund Univ, Skane Univ Hosp, Lund, Sweden. Sahlgrens Acad, Gothenburg, Sweden. Univ Hosp, Gothenburg, Sweden. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Helsinki, Helsinki, Finland. Rigshosp, DBCG Secretariat, DK-2100 Copenhagen, Denmark. Univ Hosp, Landspitali, Reykjavik, Iceland. Akershus Univ Hosp, Lorenskog, Norway. Orebro Univ Hosp, Orebro, Sweden. Uppsala Univ, Akad Hosp, Uppsala, Sweden.. - 0008-5472 .- 1538-7445. ; 76
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Journal article (other academic/artistic)
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Aesoy, R., et al.
(author)
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An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells
- 2008
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In: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 6:10, s. 1630-1638
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Journal article (peer-reviewed)abstract
- Tamoxifen, a partial estrogen receptor antagonist, is part of the standard treatment of both primary and advanced breast cancers. However, significant proportions of breast cancers are either de novo resistant or develop tamoxifen resistance during the course of treatment through mechanisms which have been only partly characterized. We have previously found that high vascular endothelial growth factor (VEGF) or VEGF receptor 2 (VEGFR2) expression and concomitant high p38 mitogen-activated protein kinase activity within breast cancers predict a poor outcome for tamoxifen-treated patients. Here, we have molecularly dissected how VEGF/VEGFR2 and p38 are linked, and contribute to tamoxifen resistance within breast cancer using a MCF-7 BC cell model with different 4-hydroxytamoxifen (4-OHT) responsiveness. We report that MCF-7 breast cancer cell lines with tamoxifen resistance have increased secretion of VEGF and increased signaling through VEGFR2 compared with parental MCF-7 cells. 4-OHT treatment caused the ablation of VEGF secretion in parental MCF-7 cells, whereas in the tamoxifen-resistant subline, a VEGF/ VEGFR2 signaling loop was still evident upon treatment. Increased basal levels of total and phosphorylated p38 were observed in tamoxifen-resistant cells. Pharmacologic inhibition of p38 reduced the proliferation of both tamoxifen-responsive and tamoxifen-resistant cells and showed an additive growth-inhibitory effect in combination with 4-OHT. A connection between VEGF/ VEGFR2 and p38 signaling was identified by VEGF and VEGFR2 knockdown, which equally reduced both the total and the active forms of p38 in tamoxifen-resistant cells. Taken together, our results suggest that decreased sensitivityto 4-OHT is caused by a death-protecting VEGF/VEGFR2 and p38 growth factor loop in breast cancer cells. Inhibition of these signaling pathways may be beneficial to overcome tamoxifen resistance. Copyright © 2008 American Association for Cancer Research.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Bjohle, J, et al.
(author)
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Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
- 2013
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In: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
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Journal article (peer-reviewed)abstract
- The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Cardoso, F., et al.
(author)
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Characterization of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program
- 2018
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:2, s. 405-417
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Journal article (peer-reviewed)abstract
- Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥ 3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+(P=0.001), highly PR+(P=0.002), highly AR+ disease (P=0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in > 90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
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- Chen, Deliang, 1961, et al.
(author)
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Recent Recovery of the Siberian High Intensity
- 2011
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 116
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Journal article (peer-reviewed)abstract
- This study highlights the fast recovery of the wintertime Siberian High intensity (SHI) over the last two decades. The SHI showed a marked weakening trend from the 1970s to 1980s, leading to unprecedented low SHI in the early 1990s according to most observational data sets. This salient declining SHI trend, however, was sharply replaced by a fast recovery over the last two decades. Since the declining SHI trend has been considered as one of the plausible consequences of climate warming, the recent SHI recovery seemingly contradicts the continuous progression of climate warming in the Northern Hemisphere. We suggest that alleviated surface warming and decreased atmospheric stability in the central Siberia region, associated with an increase in Eurasian snow cover, in the recent two decades contributed to this rather unexpected SHI recovery. The prominent SHI change, however, is not reproduced by general circulation model (GCM) simulations used in the IPCC AR4. The GCMs indicate the steady weakening of the SHI for the entire 21st century, which is found to be associated with a decreasing Eurasian snow cover in the simulations. An improvement in predicting the future climate change in regional scale is desirable.
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- Chen, F., et al.
(author)
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Juniper Tree-Ring Data from the Kuramin Range (Northern Tajikistan) Reveals Changing Summer Drought Signals in Western Central Asia
- 2019
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In: Forests. - : MDPI AG. - 1999-4907. ; 10:6
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Journal article (peer-reviewed)abstract
- Coniferous forests cover the mountains in many parts of Central Asia and provide large potentials for dendroclimatic studies of past climate variability. However, to date, only a few tree-ring based climate reconstructions exist from this region. Here, we present a regional tree-ring chronology from the moisture-sensitive Zeravshan juniper (Juniperus seravschanica Kom.) from the Kuramin Range (Tajikistan) in western Central Asia, which is used to reveal past summer drought variability from 1650 to 2015 Common Era (CE). The chronology accounts for 40.5% of the variance of the June-July self-calibrating Palmer Drought Severity Index (scPDSI) during the instrumental period (1901 to 2012). Seven dry periods, including 1659-1696, 1705-1722, 1731-1741, 1758-1790, 1800-1842, 1860-1875, and 1931-1987, and five wet periods, including 1742-1752, 1843-1859, 1876-1913, 1921-1930, and 1988-2015, were identified. Good agreements between drought records from western and eastern Central Asia suggest that the PDSI records retain common drought signals and capture the regional dry/wet periods of Central Asia. Moreover, the spectral analysis indicates the existence of centennial (128 years), decadal (24.3 and 11.4 years), and interannual (8.0, 3.6, 2.9, and 2.0 years) cycles, which may be linked with climate forces, such as solar activity and El Nino-Southern Oscillation (ENSO). The analysis between the scPDSI reconstruction and large-scale atmospheric circulations during the reconstructed extreme dry and wet years can provide information about the linkages of extremes in our scPDSI record with the large-scale ocean-atmosphere-land circulation systems.
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- Colleoni, M., et al.
(author)
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Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
- 2016
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 34:28, s. 3400-9
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Journal article (peer-reviewed)abstract
- Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population. (C) 2016 by American Society of Clinical Oncology.
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