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Sökning: WFRF:(O'Brien Stephen)

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1.
  • Bentley, Michael J., et al. (författare)
  • A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
  • 2014
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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2.
  • Abdoullaye, Doukary, et al. (författare)
  • Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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3.
  • Adewumi, Oluseun, et al. (författare)
  • Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
  • 2007
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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4.
  • Axfors, Cathrine, et al. (författare)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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5.
  • Barnett, Ross, et al. (författare)
  • Genomic Adaptations and Evolutionary History of the Extinct Scimitar-Toothed Cat, Homotherium latidens
  • 2020
  • Ingår i: Current Biology. - 0960-9822 .- 1879-0445.
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Homotherium was a genus of large-bodied scimitar-toothed cats, morphologically distinct from any extant felid species, that went extinct at the end of the Pleistocene [1, 2, 3, 4]. They possessed large, saber-form serrated canine teeth, powerful forelimbs, a sloping back, and an enlarged optic bulb, all of which were key characteristics for predation on Pleistocene megafauna [5]. Previous mitochondrial DNA phylogenies suggested that it was a highly divergent sister lineage to all extant cat species [6, 7, 8]. However, mitochondrial phylogenies can be misled by hybridization [9], incomplete lineage sorting (ILS), or sex-biased dispersal patterns [10], which might be especially relevant for Homotherium since widespread mito-nuclear discrepancies have been uncovered in modern cats [10]. To examine the evolutionary history of Homotherium, we generated a ∼7x nuclear genome and a ∼38x exome from H. latidens using shotgun and target-capture sequencing approaches. Phylogenetic analyses reveal Homotherium as highly divergent (∼22.5 Ma) from living cat species, with no detectable signs of gene flow. Comparative genomic analyses found signatures of positive selection in several genes, including those involved in vision, cognitive function, and energy consumption, putatively consistent with diurnal activity, well-developed social behavior, and cursorial hunting [5]. Finally, we uncover relatively high levels of genetic diversity, suggesting that Homotherium may have been more abundant than the limited fossil record suggests [3, 4, 11, 12, 13, 14]. Our findings complement and extend previous inferences from both the fossil record and initial molecular studies, enhancing our understanding of the evolution and ecology of this remarkable lineage.
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6.
  • Brennan, Donal J, et al. (författare)
  • Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer
  • 2008
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; 14:9, s. 2681-2689
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.
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7.
  • De Vleeschouwer, David, et al. (författare)
  • The amplifying effect of Indonesian Throughflow heat transport on Late Pliocene Southern Hemisphere climate cooling
  • 2018
  • Ingår i: Earth and Planetary Science Letters. - : ELSEVIER SCIENCE BV. - 0012-821X .- 1385-013X. ; 500, s. 15-27
  • Tidskriftsartikel (refereegranskat)abstract
    • An unusually short glaciation interrupted the warm Pliocene around 3.3 Ma (Marine Isotope Stage (MIS) M2). Different hypotheses exist to explain why this glaciation event was so pronounced, and why the global climate system returned to warm Pliocene conditions relatively quickly afterwards. One of these proposed mechanisms is a reduced equator-to-pole heat transfer, in response to a tectonically reduced Indonesian Throughflow (ITF). The ITF is a critical part of the global thermohaline ocean circulation, transporting heat from the Indo-Pacific Warm Pool to the Indian Ocean. When ITF connectivity is reduced, the water and heat supply for the Leeuwin Current, flowing poleward along Australia's west coast, is also diminished. To assess the possible relationship between mid-Pliocene glaciations and latitudinal heat transport through the Indonesian Throughflow, we constructed a multi-proxy orbital scale record for the 3.7-2.8 Ma interval from International Ocean Discovery Program (IODP) Site U1463, off northwest Australia. The comparison of the Site U1463 record with paleoclimate records from nearby Site 763 and West Pacific Warm Pool Site 806 allows for a detailed regional reconstruction of Pliocene paleoceanography and thus for testing the proposed hypothesis. An astronomically-paced decrease in potassium content characterizes the late Pliocene interval of U1463. This record documents the increasing aridity of northwest Australia, periodically alleviated by reinforced summer monsoon precipitation under summer insolation maxima. The 3180 record of the planktonic foraminifer Globigerinoides sacculifer correlates exceptionally well with the sea surface temperature (SST) record from Site 806 in the West Pacific Warm Pool, even during MIS M2. Hence, Site U1463 preserves an uninterrupted ITF signal even during Pliocene glaciations. However, the U1463 delta O-18(G.sacculifer) record exhibits a 0.5 parts per thousand offset with the nearby Site 763A record around MIS M2. This implies that Site 763A, about 500 km west of U1463, more closely tracks Indian Ocean SST records across MIS M2. The U1463 data reveal that heat-transport through the Indonesian Throughflow did not shut down completely during MIS M2, but rather its intensity decreased prior to and during MIS M2, causing Site 763A to temporarily reflect an Indian Ocean, rather than an ITF signal. We conclude that ITF variability significantly influenced latitudinal heat transport by means of the Leeuwin Current and hence contributed to the relative intensity of MIS M2. We propose the ITF valve between the Pacific and Indian Ocean as a positive feedback mechanism, in which an initial sea level lowering reduces ITF heat transport, in turn amplifying global cooling by advancing the thermal isolation of Antarctica.
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8.
  • Druker, Brian J., et al. (författare)
  • Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
  • 2006
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
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9.
  • Engel, Lawrence S., et al. (författare)
  • Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer : A case–control study nested within two prospective cohorts
  • 2019
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:9, s. 2360-2371
  • Tidskriftsartikel (refereegranskat)abstract
    • Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case–control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p’-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p’-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.
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10.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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