The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a ...drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
Coastal and estuarine wetlands provide a range of important ecosystem services, but are currently being damaged and degraded due to human activities, reduced sediment supply and sea level rise. ...Managed realignment (MR) is one approach used to compensate for the loss of intertidal habitat, however saltmarshes in MR sites have been recognised to have lower biodiversity than natural environments. This has been associated with differences in the physical functioning including the sediment structure, reduced hydraulic connectivity, and lower topographic variability such as the abundance of intertidal creek networks. Intertidal morphology, including creek networks, play an important role in supporting and regulating saltmarsh environments through the supply of sediment, nutrients and water, and in draining intertidal marshes. However, there is a lack of empirical data on the formation and evolution of topographic features and variability in saltmarsh environments. This is likely to be due to creek networks in natural marshes already being in a state of quasi-equilibrium, making MR sites an ideal environment to investigate creek development. However, traditional remote sensing techniques (such as LiDAR) tend to be relatively expensive, infrequent and at a coarse resolution meaning small, but important (cm-scale), changes are often missed. This study advances the ability to detect these small scale changes by demonstrating the suitability and potential applications of using the emerging photogrammetric method Structure-from-Motion (SfM) on images taken using a small-Unmanned Aerial System (sUAS). Three surveys from a rapidly changing, near-breach site were taken at the Medmerry Managed Realignment Site in July 2016, September 2017 and July 2018. A suitable degree of confidence was found between the modelled surface and independent check points (vertical root-mean-square-errors of 0.0245, 0.0704 and 0.1571 for 2016, 2017 and 2018 respectively). DSMs of Difference (DoD) analysis was performed to evaluate elevation change, with areas experiencing up to 85 cm of accretion between 2016 and 2018. However, when considering the error associated with both surveys, between 2016 and 2017, only 34.39% of the survey area experienced change above the level of detection (LoD). In contrast, 76.97% experienced change greater than the LoD between 2017 and 2018. Stream order analysis classified the creek networks into five orders in 2016 and four orders in 2017 and 2018, with 2016 having a higher abundance (291 in 2016 compared to 117 (2017) and 112 (2018)) and density (0.44 m/m2 in 2016 compared to 0.27 m/m2 in both 2017 and 2018) of creek networks. These results provide an innovative high resolution insight into the evolution of restored intertidal wetlands, and suggest that SfM analysis of images taken using a sUAS can be a useful tool with the potential to be incorporated into studies of MR and natural saltmarsh sites. sUAS analysis can, therefore, advance the management of these environments to ensure the provision of ecosystem services and to protect against future anthropogenic activity, sea level rise and climate change.
Managed Realignment (MR) schemes are considered by many coastal managers and engineers to be a preferable method of coastal flood defence and compensating for habitat loss, by creating new areas of ...intertidal saltmarsh and mudflat habitat. Monitoring of MR sites has tended to focus on short term ecological factors, resulting in a shortage of high frequency, high resolution long term measurements of the evolution of the sediment erosion, transportation, deposition and consolidation cycle (ETDC) in newly breached sites. This is particularly true of analysis of the formation and preservation of sedimentary rhythmites and evaluations of sedimentation rates (and their variability) in newly inundated intertidal environments. This study provides an evaluation of sedimentation rhythms and hydrodynamics from two contrasting sites within the Medmerry Managed Realignment scheme, the largest open coast realignment in Europe (at the time of site inundation). Bed sediment altimeter data highlighted different sedimentation patterns at the two sites; near constant deposition of sediment occurred near the breach resulting in 15.2cm of sediment being accreted over the one year monitoring period, whereas periodic accretion and erosion of sediment occurred inland leading to 2.7cm of net accretion. Differences in the relationship between suspended sediment concentrations and site hydrodynamics were observed on a semi-diurnal to annual scale. This study highlights the need for further consideration of the sedimentation processes in MR schemes in order to enhance the design and construction of these sites. Advancements in the understanding of these processes will increase the success of MR schemes in terms of the evolution of the sediment regime and the ecosystem services provided, particularly as they are more widely accepted as a form of coastal flood defence and intertidal habitat creation method.
•Sedimentation rhythms at a major managed realignment site are examined.•Different sedimentation patterns were found at two heavily engineered sites.•Freshwater input and site design controlled the supply and transfer of sediment.•Understanding of sedimentation processes is required to enhance site design.
Managed realignment (MR) schemes are being implemented to compensate for the loss of intertidal saltmarsh habitats by breaching flood defences and inundating the formerly defended coastal hinterland. ...However, studies have shown that MR sites have lower biodiversity than anticipated, which has been linked with anoxia and poor drainage resulting from compaction and the collapse of sediment pore space caused by the site's former terrestrial land use. Despite this proposed link between biodiversity and soil structure, the evolution of the sediment sub-surface following site inundation has rarely been examined, particularly over the early stages of the terrestrial to marine or estuarine transition. This paper presents a novel combination of broad- and intensive-scale analysis of the sub-surface evolution of the Medmerry Managed Realignment Site (West Sussex, UK) in the three years following site inundation. Repeated broad-scale sediment physiochemical datasets are analysed to assess the early changes in the sediment subsurface and the preservation of the former terrestrial surface, comparing four locations of different former land uses. Additionally, for two of these locations, high-intensity 3D-computed X-ray microtomography and Itrax micro-X-ray fluorescence spectrometry analyses are presented. Results provide new data on differences in sediment properties and structure related to the former land use, indicating that increased agricultural activity leads to increased compaction and reduced porosity. The presence of anoxic conditions, indicative of poor hydrological connectivity between the terrestrial and post-inundation intertidal sediment facies, was only detected at one site. This site has experienced the highest rate of accretion over the terrestrial surface (ca. 7 cm over 36 months), suggesting that poor drainage is caused by the interaction (or lack of) between sediment facies rather than the former land use. This has significant implications for the design of future MR sites in terms of preparing sites, their anticipated evolution, and the delivery of ecosystem services.
Schematic comparison of the sub-surface physicochemical properties of the sediment found at the Medmerry Managed Realignment Site (this study), Orplands Farm Managed Realignment Site, U.K. (Spencer et al., 2008; Tempest et al., 2015; Spencer et al., 2017) and a typical natural minerogenic saltmarsh (Cundy and Croudace, 1995). Not drawn to uniform vertical scale. Display omitted
•Sediment properties and structure differ in relation to the former land use.•Anoxic conditions only detected at site with highest sediment accretion rate.•Poor drainage is caused by the lack of interaction between sediment facies.•Findings important for predicting the delivery of ecosystem services in future sites.
Managed realignment (MR) sites are being implemented to compensate for the loss of natural saltmarsh habitat due to sea level rise and anthropogenic pressures. However, MR sites have been recognised ...to have lower morphological variability and coverage of saltmarsh vegetation than natural saltmarsh sites, which have been linked with the legacy of the historic (terrestrial) land use. This study assesses the relationship between the morphology and vegetation coverage in three separate zones, associated with the legacy of historic reclamation, of a non-engineered MR site. The site was selected due to the phased historical reclamation, and because no pre-breaching landscaping or engineering works were carried out prior to the more recent and contemporary breaching of the site. Four vegetation indices (Excess Green Index, Green Chromatic Coordinate, Green-Red Vegetation Index, and Visible Atmospherically Resistant Index) were calculated from unmanned aerial vehicle imagery; elevation, slope, and curvature surface models were calculated from a digital surface model (DSM) generated from the same imagery captured at the MR site. The imagery and DSM summarised the three zones present within the MR site and the adjacent external natural marsh, and were used to examine the site for areas of differing vegetation cover. Results indicated statistically significant differences between the vegetation indices across the three zones. Statistically significant differences in the vegetation indices were also found between the three zones and the external natural saltmarsh. However, it was only in the zone nearest the breach, and for three of the four indices, that a moderate to strong correlation was found between elevation and the vegetation indices (r = 0.53 to 0.70). This zone was also the lowest in elevation and exhibited the lowest average value for all indices. No relationship was found between the vegetation indices and either the slope or curvature in any of the zones. The approach outlined in this paper provides coastal managers with a relatively low-cost, low-field time method of assessing the areas of vegetation development in MR sites. Moreover, the findings indicate the potential importance of considering the historic morphological and sedimentological changes in the MR sites. By combining data on the areas of saltmarsh colonisation with a consideration of the site’s morphological and reclamation history, the areas likely to support saltmarsh vegetation can be remotely identified in the design of larger engineered MR sites maximising the compensation for the loss of saltmarsh habitat elsewhere.
Despite the 2009 World Health Organization recommendation that all countries introduce rotavirus vaccines (RVV) into their national immunization programs, just 81 countries had introduced RVV by the ...end of 2015, leaving millions of children at risk for rotavirus morbidity and mortality. In response, the Rotavirus Accelerated Vaccine Introduction Network (RAVIN) was established in 2016 to provide support to eight Gavi-eligible countries that had yet to make an RVV introduction decision and/or had requested technical assistance with RVV preparations: Afghanistan, Bangladesh, Benin, Cambodia, Democratic Republic of Congo, Lao People's Democratic Republic, Myanmar, and Nepal. During 2016-2020, RAVIN worked with country governments and partners to support evidence-based immunization decision-making, RVV introduction preparation and implementation, and multilateral coordination. By the September 2020 program close-out, five of the eight RAVIN focus countries successfully introduced RVV into their routine childhood immunization programs. We report on the RAVIN approach, describe how the project responded collectively to an evolving RVV product landscape, synthesize common characteristics of the RAVIN country experiences, highlight key lessons learned, and outline the unfinished agenda to inform future new vaccine introduction efforts by countries and global partners.
There is growing evidence that managed realignment (MR) sites have lower biodiversity than natural saltmarshes, which has been associated with differences in the physical function and morphological ...evolution following site breaching. This evidence has been derived from MR sites previously used for intensive arable agriculture or modified during site construction. Therefore, the development of these sites may not be representative of the sedimentological evolution that would have otherwise occurred. This paper presents analysis of high spatial resolution digital surface models derived from the images collected using a small-unmanned aerial system from a non-engineered MR site at Cwm Ivy Marsh, Gower Peninsula, Wales. These models are examined alongside a novel combination of high frequency measurements of the rate and patterns of sedimentation, suspended sediment concentration (SSC), and the sub-surface structure and geochemical profiles. Results indicated that although the site became topographically less variable over a four year period, the intertidal morphology developed through an increase in the abundance of higher order creek systems and sediment being deposited at a rate of between 3 and 7 cm/year. The SSC followed an inverse pattern to water depth, with bed elevation increasing and then decreasing during both the flood and ebb tidal phases. Analysis of the sediment subsurface geochemical composition indicated redox profiles similar to natural intertidal environments; evidence of a fluctuating water table was found at a saltmarsh site, in comparison to waterlogging identified at an anoxic mudflat site. These findings provide a new insight to the sedimentological processes in a MR site without the influence of landscaping or site engineering prior to site breaching, which can be used to inform the design of future MR sites.
•Sedimentological processes in a none engineered managed realignment sites investigated.•Results indicated a sedimentation rate of between 30 and 75 mm/year.•Similar geochemical profiles to natural sites identified.•Findings inform the design of future sites for maximum ecosystem service delivery.
Managed Realignment (MR) is becoming increasingly popular with many coastal managers and engineers. Monitoring of MR sites has provided growing evidence that many of the saltmarshes created in these ...environments have lower biodiversity than naturally formed intertidal marshes, and may not fully deliver the anticipated ecosystem services such as carbon sequestration and coastal flood defence. Despite the importance of the sedimentary environment in developing an intertidal morphology suitable for plant establishment and succession, the evolution of the sediment erosion, transportation, deposition and consolidation cycle in newly breached sites is rarely examined. This study evaluates the hydrodynamics and concentration of suspended sediment exported and imported along the main drainage channel within the Medmerry Managed Realignment Site, West Sussex, UK, the largest open coast realignment in Europe (at the time of breaching). Measurements were taken over a one year period (November 2015–October 2016) at the breach, at the landwards extremity where freshwater drains into the site, and in an excavated channel in the centre of the site. At the latter site, 1.7 cm of sediment accreted over the study period. Suspended sediment concentration (SSC) measurements indicate that, under ambient conditions, sediment is imported into and exported from the Medmerry site, although similar concentrations of sediment were recorded being internally redistributed around the site (typically 0.11 g/l measured in the breach area compared to 0.12 g/l measured in the centre of the site). Sediment is removed from the site following large (1–2 mm/hour) rainfall events, which take several tidal cycles to drain through the site. Peaks in SSC corresponding with lower intensity rainfall events, especially during periods when the intertidal mudflats have been exposed, have also been observed. Analysis of the hydrodynamics and patterns of sedimentation during and following storm occurrences (the 2015-16 Storms Eva, Imogen and Katie) however demonstrate the relative resilience (i.e. rapid recovery and minimal disturbance) of the site to extreme storm events.
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Managed realignment (MR) schemes are being implemented to compensate for the degradation of coastal habitats. However, evidence suggests that MR sites have lower biodiversity than anticipated, which ...has been linked to poor drainage. Despite creek networks playing an important role in enhancing site drainage in natural intertidal environments, there remains a shortage of data on the formation and evolution of creeks within MR sites. This study evaluates creek development at the Medmerry Managed Realignment Site, UK. Creek development is investigated using differential global positioning system (dGPS) data, supported by sedimentological analyses and a high-resolution digital surface model (DSM) derived from images taken using a small unmanned aerial vehicle. Measurements indicated that creeks will develop relatively quickly, but are influenced by differences in the sub-surface sedimentological conditions. A suitable level of agreement was found between the DSM and dGPS measurements, demonstrating the appropriateness of this method to study creek development within intertidal environments at a higher resolution than traditional surveying techniques. These results are used to propose the collapse of sub-surface piping as the primary creek formation mechanism. Findings are discussed in terms of increasing the success of MR schemes and enhancing site design to maximise the ecosystem services provided.
Preliminary analysis of results from a series of studies of fine sediment transport in the macrotidal Pagham Harbour (U.K.) have revealed patterns of sediment transport which are related to tidal ...range and wind speed. This paper will present an analysis of some preliminary results from continuous monitors from two sites, which logged turbidity, salinity, water level and wind speed/direction at a frequency of 10 minutes or less. At one site in particular (the Ferry Pool site), detailed results of the variation in salinity and suspended sediment concentration with depth, and near-bed flow velocity, are presented. In general, shorter, faster flood-tide currents lead to concentrations of suspended sediment which are highest during the first 90 minutes of the flood tide. These decrease rapidly due to settling, during the relatively low velocities around the time of high slack water. The magnitude of the peak flood-tide suspended sediment concentrations appear to correlate more with tidal range, than with wind speed, pointing to a greater sediment mobility during spring tides. Further analysis of the variation in salinity and suspended sediment concentration with depth reveal that these high flood tide suspended solids concentrations are related to short-lived local peaks, both of near-bed velocity and of vertical salinity gradient. Rapid settling of sediment occurs following flow deceleration and vertical mixing of the water with respect to salinity. It is suggested that this mechanism is of great importance in describing the landwart transport of fine sediment in harbours of this kind.
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