| 1. |
- Turkington, RC, et al.
(författare)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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| 2. |
- Allen, G., et al.
(författare)
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South East Pacific atmospheric composition and variability sampled = ong 20 degrees S during VOCALS-REx
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:11, s. 5237-5262
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Tidskriftsartikel (refereegranskat)abstract
- The VAMOS Ocean-Cloud-Atmosphere-Land Regional Experiment (VOCALS-REx) was conducted from 15 October to 15 November 2008 in the South East Pacific (SEP) region to investigate interactions between land, sea and atmosphere in this unique tropical eastern ocean environment and to improve the skill of global and regional models in = presenting the region. This study synthesises selected aircraft, ship = d surface site observations from VOCALS-REx to statistically summarise = d characterise the atmospheric composition and variability of the = rine Boundary Layer (MBL) and Free Troposphere (FT) along the 20 = grees S parallel between 70 degrees W and 85 degrees W. Significant = nal gradients in mean MBL sub-micron aerosol particle size and = mposition, carbon monoxide, sulphur dioxide and ozone were seen over = e campaign, with a generally more variable and polluted coastal = vironment and a less variable, more pristine remote maritime regime. = adients in aerosol and trace gas concentrations were observed to be = sociated with strong gradients in cloud droplet number. The FT was = ten more polluted in terms of trace gases than the MBL in the mean; = wever increased variability in the FT composition suggests an episodic = ture to elevated concentrations. This is consistent with a complex = rtical interleaving of airmasses with diverse sources and hence = llutant concentrations as seen by generalised back trajectory = alysis, which suggests contributions from both local and long-range = urces. Furthermore, back trajectory analysis demonstrates that the = served zonal gradients both in the boundary layer and the free = oposphere are characteristic of marked changes in airmass history with = stance offshore - coastal boundary layer airmasses having been in = cent contact with the local land surface and remote maritime airmasses = ving resided over ocean for in excess of ten days. Boundary layer = mposition to the east of 75 degrees W was observed to be dominated by = astal emissions from sources to the west of the Andes, with evidence = r diurnal pumping of the Andean boundary layer above the height of the = rine capping inversion. Analysis of intra-campaign variability in = mospheric composition was not found to be significantly correlated = th observed low-frequency variability in the large scale flow pattern; = mpaign-average interquartile ranges of CO, SO(2) and O(3) = ncentrations at all longitudes were observed to dominate over much = aller differences in median concentrations calculated between periods = different flow regimes. The campaign climatology presented here aims = provide a valuable dataset to inform model simulation and future = ocess studies, particularly in the context of aerosol-cloud = teraction and further evaluation of dynamical processes in the SEP = gion for conditions analogous to those during VOCALS-REx. To this end, = r results are discussed in terms of coastal, transitional and remote = atial regimes in the MBL and FT and a gridded dataset are provided as = resource.
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| 3. |
- Bribiesca-Contreras, G., et al.
(författare)
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Benthic megafauna of the western Clarion-Clipperton Zone, Pacific Ocean
- 2022
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Ingår i: Zookeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :1113, s. 1-110
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest in the exploitation of deep-sea mineral deposits, particularly on the abyssal seafloor of the central Pacific Clarion-Clipperton Zone (CCZ), which is rich in polymetallic nodules. In order to effectively manage potential exploitation activities, a thorough understanding of the biodiversity, community structure, species ranges, connectivity, and ecosystem functions across a range of scales is needed. The benthic megafauna plays an important role in the functioning of deep-sea ecosystems and represents an important component of the biodiversity. While megafaunal surveys using video and still images have provided insight into CCZ biodiversity, the collection of faunal samples is needed to confirm are very rarely carried out. Using a Remotely Operated Vehicle, 55 specimens of benthic megafauna were-collected from seamounts and abyssal plains in three Areas of Particular Environmental Interest (APEI 1, APEI 4, and APEI 7) at 3100-5100 m depth in the western CCZ. Using both morphological and molecular evidence, 48 different morphotypes belonging to five phyla were found, only nine referrable to known species, and 39 species potentially new to science. This work highlights the need for detailed taxonomic studies incorporating genetic data, not only within the CCZ, but in other bathyal, abyssal, and hadal regions, as representative genetic reference libraries that could facilitate the generation of species inventories.
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| 4. |
- Copus, Andrew K, et al.
(författare)
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One Size Fits All? : Regional Differentiation and Rural Development Policy
- 2007
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Ingår i: EuroChoices. - 1478-0917 .- 1746-692X. ; 6:3, s. 13-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Since enlargement the European Union has become more diverse in many socio-economic, demographic and agricultural respects. A recent research project sponsored by DG Agriculture (SERA - Study on Employment in Rural Areas) carried out a review of a broad range of regional statistics relating to rural labour markets. The results were presented within the framework of the OECD rural-urban classification. A broad overview of the findings confirms the importance of two widely acknowledged processes of change, urbanisation and counter-urbanisation. Overlaying these urban-based centripetal and centrifugal processes both east-west and north-south differentiation affects particular socio-economic aspects. The net result of this complex combination of (macro-scale) processes is a tendency for accumulation of human capital in accessible significantly rural (SR) regions and a depletion of the remoter, sparsely populated predominantly rural (PR) regions. The emphasis upon macro-scale patterns and trends complements the recent preoccupation of much rural development research upon localised 'soft factors'. There is arguably scope for both in the design of rural policy Broad spatial processes should influence resource allocation, whilst localised advantages, such as strong human and social capital, good governance, networking, clusters and networks, entrepreneurial culture, and so on, can form the basis of strategies for intervention.
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| 5. |
- Glover, AG, et al.
(författare)
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The London Workshop on the Biogeography and Connectivity of the Clarion-Clipperton Zone
- 2016
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Ingår i: Research Ideas and Outcomes. - : Pensoft Publishers. - 2367-7163. ; 2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Recent years have seen a rapid increase in survey and sampling expeditions to the Clarion-Clipperton Zone (CCZ) abyssal plain, a vast area of the central Pacific that is currently being actively explored for deep-sea minerals (ISA, 2016). Critical to the development of evidence-based environmental policy in the CCZ are data on the biogeography and connectivity of species at a CCZ-regional level. New information The London Workshop on the Biogeography and Connectivity of the CCZ was convened to support the integration and synthesis of data from European Union (EU) CCZ projects, supported by the EU Managing Impacts of Deep-Sea Resource Exploitation (MIDAS) and EU Joint Programming Initiative Healthy and Productive Seas and Oceans (JPI Oceans) projects. The London Workshop had three clear goals: (1) To explore, review and synthesise the latest molecular biogeography and connectivity data from across recent CCZ cruises from both contractor and academia-funded projects; (2) To develop complementary and collaborative institutional and program-based academic publication plans to avoid duplication of effort and ensure maximum collaborative impact; (3) To plan a joint synthetic data publication highlighting key results from a range of planned molecular biogeography/connectivity publications. 32 participants attended the workshop at the Natural History Museum in London from 10-12 May 2016. Presentations and discussions are summarised in this report covering (1) overviews of current CCZ environmental projects, (2) policy and industry perspectives, (3) synthesis of DNA taxonomy and biogeography studies, (4) summaries of the latest population genetic studies, (5) summaries of the latest broader morphological context, (6) an overview of publication and proposal plans to maximise collaborative opportunities and finally a series of workshop recommendations.
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| 8. |
- Zardi, G.I., et al.
(författare)
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Sand and wave induced mortality in invasive (Mytilus galloprovincialis) and indigenous (Perna perna) mussels.
- 2008
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Ingår i: MARINE BIOLOGY. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 153:5, s. 853-858
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Tidskriftsartikel (refereegranskat)abstract
- The ability of an invasive species to spread in a new locality depends on its interaction with the indigenous community and on variation in time and space in the environment. The Mediterranean mussel Mytilus galloprovincialis invaded the South African coast 30 years ago and it now competes and coexists with the indigenous mussel Perna perna. The two species show different tolerances to wave and sand stress, two of the main environmental factors affecting this intertidal community. P. perna is more resistant to hydrodynamic stress than M. galloprovincialis, while the invasive species is less vulnerable to sand action. Our results show that mortality rates of the two species over a period of 6 months had different timing. The indigenous species had higher mortality than M. galloprovincialis during periods of high sand accumulation in mussel beds, while the pattern reversed during winter, when wave action was high. A negative correlation between sand accumulation and attachment strength of the two mussels showed that sand not only affects mussel mortality through scouring and burial, but also weakens their attachment strength, subjecting them to a higher risk of dislodgement. Here we underline the importance of variations in time and space of environmental stress in regulating the interaction between invasive and indigenous species, and how these variations can create new competitive balances.
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