Miocene restriction of the Pacific-North Atlantic throughflow strengthened Atlantic overturning circulation

Export of warm and salty waters from the Caribbean to the North Atlantic is an essential component of the Atlantic Meridional Overturning Circulation (AMOC). However, there was also an active AMOC during the Miocene, despite evidence for an open Central American Seaway (CAS) that would have allowed low-salinity Pacific waters to enter the Caribbean. To address this apparent contradiction and to constrain the timing of CAS closure we present the first continuous Nd isotope record of intermediate waters in the Florida Strait over the past 12.5 million years. Our results indicate that there was no direct intermediate water mass export from the Caribbean to the Florida Strait between 11.5 and 9.5 Ma, at the same time as a strengthened AMOC. After 9 Ma a strong AMOC was maintained due to a major step in CAS closure and the consequent cessation of low-salinity Pacific waters entering the Caribbean

The influence of basaltic islands on the oceanic REE distribution: A case study from the tropical South Pacific

The Rare Earth Elements (REEs) have been widely used to investigate marine biogeochemical processes as well as the sources and mixing of water masses. However, there are still important uncertainties about the global aqueous REE cycle with respect to the contributions of highly reactive basaltic minerals originating from volcanic islands and the role of Submarine Groundwater Discharge (SGD). Here we present dissolved REE concentrations obtained from waters at the island-ocean interface (including SGD, river, lagoon and coastal waters) from the island of Tahiti and from three detailed open ocean profiles on the Manihiki Plateau (including neodymium (Nd) isotope compositions), which are located in ocean currents downstream of Tahiti. Tahitian fresh waters have highly variable REE concentrations that likely result from variable water–rock interaction and removal by secondary minerals. In contrast to studies on other islands, the SGD samples do not exhibit elevated REE concentrations but have distinctive REE distributions and Y/Ho ratios. The basaltic Tahitian rocks impart a REE pattern to the waters characterized by a middle REE enrichment, with a peak at europium similar to groundwaters and coastal waters of other volcanic islands in the Pacific. However, the basaltic island REE characteristics (with the exception of elevated Y/Ho ratios) are lost during transport to the Manihiki Plateau within surface waters that also exhibit highly radiogenic Nd isotope signatures. Our new data demonstrate that REE concentrations are enriched in Tahitian coastal water, but without multidimensional sampling, basaltic island Nd flux estimates range over orders of magnitude from relatively small to globally significant. Antarctic Intermediate Water (AAIW) loses its characteristic Nd isotopic signature (-6 to-9) around the Manihiki Plateau as a consequence of mixing with South Equatorial Pacific Intermediate Water (SEqPIW), which shows more positive values (-1 to -2). However, an additional Nd input/exchange along the pathway of AAIW, eventually originating from the volcanic Society, Tuamotu and Tubuai Islands (including Tahiti), is indicated by an offset from the mixing array of AAIW and SEqPIW to more radiogenic Nd isotope compositions

Late Pliocene and Early Pleistocene variability of the REE and Nd isotope composition of Caribbean bottom water: A record of changes in sea level and terrestrial inputs during the final stages of Central American Seaway closure

The isotopic composition of neodymium dissolved in seawater consists of a distal, advected component that reflects water mass mixing and circulation, but near land can also contain a large local component originating from terrestrial sources such as aeolian or fluvial material. In order to use Nd isotopes to reconstruct paleocirculation, it is important to detect any local influences on the seawater signal recorded in deep sea sediments. Here we present rare earth element (REE) and Nd isotope (εNd) records from the deep Caribbean for two well‐studied time intervals in the Late Pliocene and Early Pleistocene. We measured trace element and REE compositions of weakly cleaned foraminifera to investigate if the Nd isotope signal from the same samples contained a local component. We find distinct changes in REE compositions across glaciations that are consistent with increases in the supply of local terrestrial material to the basin likely the results of glacially driven changes in sea level. Despite these larger terrestrial inputs, the Ce anomaly (Ce/Ce*) became more pronounced during glaciations indicating a better deep Caribbean ventilation. Short negative Nd isotope excursions occurred during three of the four studied glaciations, independently of any other proxy indicators for changes in ocean circulation suggesting that inputs from local terrigenous sources of Nd controlled the signal. We recommend that studies that aim to use εNd as a paleocirculation tracer routinely measure REE compositions of the authigenic phase to identify any possible terrestrial influence on the signal

Major intensification of Atlantic overturning circulation at the onset of Paleogene greenhouse warmth

During the Late Cretaceous and early Cenozoic the Earth experienced prolonged climatic cooling most likely caused by decreasing volcanic activity and atmospheric CO2 levels. However, the causes and mechanisms of subsequent major global warming culminating in the late Paleocene to Eocene greenhouse climate remain enigmatic. We present deep and intermediate water Nd-isotope records from the North and South Atlantic to decipher the control of the opening Atlantic Ocean on ocean circulation and its linkages to the evolution of global climate. The marked convergence of Nd-isotope signatures 59 million years ago indicates a major intensification of deep-water exchange between the North and South Atlantic, which coincided with the turning point of deep-water temperatures towards early Paleogene warming. We propose that this intensification of Atlantic overturning circulation in concert with increased atmospheric CO2 from continental rifting marked a climatic tipping point contributing to a more efficient distribution of heat over the planet

Temperate airborne grass pollen defined by spatio-temporal shifts in community composition

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Grass pollen is the world’s most harmful outdoor aeroallergen. However, it is unknown how airborne pollen assemblages change across time and space. Human sensitivity varies between different species of grass that flower at different times, but it is not known whether temporal turnover in species composition match terrestrial flowering or whether species richness steadily accumulates over the grass pollen season. Here, using targeted, high-throughput sequencing, we demonstrate that all grass genera displayed discrete, temporally restricted peaks of incidence, which varied with latitude and longitude throughout Great Britain, revealing that the taxonomic composition of grass pollen exposure changes substantially across the grass pollen season.Natural Environment Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC

The Contribution of Social Networks to the Health and Self-Management of Patients with Long-Term Conditions: A Longitudinal Study

Evidence for the effectiveness of patient education programmes in changing individual self-management behaviour is equivocal. More distal elements of personal social relationships and the availability of social capital at the community level may be key to the mobilisation of resources needed for long-term condition self-management to be effective. Aim: To determine how the social networks of people with long-term conditions (diabetes and heart disease) are associated with health-related outcomes and changes in outcomes over time. Methods: Patients with chronic heart disease (CHD) or diabetes (n = 300) randomly selected from the disease registers of 19 GP practices in the North West of England. Data on personal social networks collected using a postal questionnaire, alongside face-to-face interviewing. Follow-up at 12 months via postal questionnaire using a self-report grid for network members identified at baseline. Analysis: Multiple regression analysis of relationships between health status, self-management and health economics outcomes, and characteristics of patients’ social networks. Results: Findings indicated that: (1) social involvement with a wider variety of people and groups supports personal self-management and physical and mental well-being; (2) support work undertaken by personal networks expands in accordance with health needs helping people to cope with their condition; (3) network support substitutes for formal care and can produce substantial saving in traditional health service utilisation costs. Health service costs were significantly (p0.01) reduced for patients receiving greater levels of illness work through their networks. Conclusions: Support for self-management which achieves desirable policy outcomes should be construed less as an individualised set of actions and behaviour and more as a social network phenomenon. This study shows the need for a greater focus on harnessing and sustaining the capacity of networks and the importance of social involvement with community groups and resources for producing a more desirable and cost-effective way of supporting long term illness management

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3)

© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).AIMS: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. METHODS: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. CONCLUSION: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.Peer reviewe

Independence of HIF1a and androgen signaling pathways in prostate cancer

Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Abstract: Background: Therapeutic targeting of the androgen signaling pathway is a mainstay treatment for prostate cancer. Although initially effective, resistance to androgen targeted therapies develops followed by disease progression to castrate-resistant prostate cancer (CRPC). Hypoxia and HIF1a have been implicated in the development of resistance to androgen targeted therapies and progression to CRCP. The interplay between the androgen and hypoxia/HIF1a signaling axes was investigated. Methods: In vitro stable expression of HIF1a was established in the LNCaP cell line by physiological induction or retroviral transduction. Tumor xenografts with stable expression of HIF1a were established in castrated and non-castrated mouse models. Gene expression analysis identified transcriptional changes in response to androgen treatment, hypoxia and HIF1a. The binding sites of the AR and HIF transcription factors were identified using ChIP-seq. Results: Androgen and HIF1a signaling promoted proliferation in vitro and enhanced tumor growth in vivo. The stable expression of HIF1a in vivo restored tumor growth in the absence of endogenous androgens. Hypoxia reduced AR binding sites whereas HIF binding sites were increased with androgen treatment under hypoxia. Gene expression analysis identified seven genes that were upregulated both by AR and HIF1a, of which six were prognostic. Conclusions: The oncogenic AR, hypoxia and HIF1a pathways support prostate cancer development through independent signaling pathways and transcriptomic profiles. AR and hypoxia/HIF1a signaling pathways independently promote prostate cancer progression and therapeutic targeting of both pathways simultaneously is warranted

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy