Salt-marsh testate amoebae as precise and widespread indicators of sea-level change

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Salt-marsh sediments are routinely used to reconstruct sea-level changes over past millennia. These reconstructions bridge an important gap between geological and instrumental sea-level records, and provide insights into the role of atmospheric, oceanic, climatic and anthropogenic sea-level drivers, thereby improving understanding of contemporary and future sea-level changes. Salt-marsh foraminifera, diatoms and testate amoebae are three of the proxies capable of accurately reconstructing former sea level over decadal to millennial timescales. Datasets of surface assemblages are collated along elevational gradients to provide modern analogues that can be used to infer former marsh-surface elevations from fossil assemblages. Testate amoebae are the most recently developed proxy and existing studies suggest that they are at least as precise as the two other proxies. This study provides a synthesis of sea-level research using testate amoebae and collates and analyses existing surface datasets of intertidal salt-marsh testate amoebae from sites throughout the North Atlantic. We test the hypothesis that intertidal testate amoebae demonstrate cosmopolitan intertidal zonation across wide geographical areas in a way that is unique to this proxy. Testate amoebae assemblages are harmonised under a unified taxonomy and standardised into a single basin-wide training set suitable for reconstructing sea-level changes from salt-marsh sediments across the North Atlantic. Transfer functions are developed using regression modelling and show comparable performance values to published local training sets of foraminifera, diatoms and testate amoebae. When used to develop recent (last 100 years) sea-level reconstructions for sites in Norway and Quebec, Canada, the testate amoebae-based transfer function demonstrated prediction uncertainties of ± 0.26 m and ± 0.10 m respectively. These uncertainties equate to 10% and 11% of the tidal ranges at each site, which is of comparable precision to other published sea-level reconstructions based on foraminifera or diatoms. There is great scope for further developing intertidal testate amoebae as precise sea-level indicators and their application should be tested at sites beyond the North Atlantic.Our work on salt-marsh testate amoebae was funded by the Natural Environment Research Council (grant GR9/03426 to WRG and DJC) and by Plymouth University studentships (to RLB and TLN). Datasets from the Magdalen Islands were originally collected using funding from the Coastal Geoscience Research Chair at the Université du Québec à Rimouski

Incorporating Genetic Biomarkers into Predictive Models of Normal Tissue Toxicity.

There is considerable variation in the level of toxicity patients experience for a given dose of radiotherapy, which is associated with differences in underlying individual normal tissue radiosensitivity. A number of syndromes have a large effect on clinical radiosensitivity, but these are rare. Among non-syndromic patients, variation is less extreme, but equivalent to a ±20% variation in dose. Thus, if individual normal tissue radiosensitivity could be measured, it should be possible to optimise schedules for individual patients. Early investigations of in vitro cellular radiosensitivity supported a link with tissue response, but individual studies were equivocal. A lymphocyte apoptosis assay has potential, and is currently under prospective validation. The investigation of underlying genetic variation also has potential. Although early candidate gene studies were inconclusive, more recent genome-wide association studies are revealing definite associations between genotype and toxicity and highlighting the potential for future genetic testing. Genetic testing and individualised dose prescriptions could reduce toxicity in radiosensitive patients, and permit isotoxic dose escalation to increase local control in radioresistant individuals. The approach could improve outcomes for half the patients requiring radical radiotherapy. As a number of patient- and treatment-related factors also affect the risk of toxicity for a given dose, genetic testing data will need to be incorporated into models that combine patient, treatment and genetic data.NGB is supported by the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.clon.2015.06.01

Exploiting biological and physical determinants of radiotherapy toxicity to individualise treatment.

This is the final version of the article. It first appeared from the British Institute of Radiology via http://dx.doi.org/10.1259/bjr.20150172The recent advances in radiation delivery can improve tumour control probability and reduce treatment related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day-to-day. Daily image guidance scans can be used to identify the position of normal tissue structures, and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues which limits radiotherapy dose and therefore tumour control. However, the dose response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of radiotherapy. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be due to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In prostate cancer patients receiving curative radiotherapy, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses (EUDs) was -2.7 Gy (5%), and a dose reduction was seen in 7/10 cases. If dose escalation were performed to take rectal dose back to the planned level, this should increase the mean tumour control probability (TCP) (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical radiotherapy who might benefit from either dose escalation, suggesting improved tumour cure, or reduced toxicity, or both.JS is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is supported by the NIHR Cambridge Biomedical Research Centre. The VoxTox Research Programme is funded by Cancer Research UK

Reliability and validity of the IPAQ-L in a sample of Hong Kong Urban older adults: does neighborhood of residence matter?

This study examined reliability and validity of the Chinese version of the International Physical Activity Questionnaire–Long Form (IPAQ-LC) in Chinese seniors, including moderating effects of neighborhood walkability and socioeconomic status (SES) on reliability and validity. The IPAQ-LC was interviewer-administered (n = 96), accelerometer and 7-day walk-diary data were collected (n = 94), and the IPAC-LC was readministered (N = 92). Acceptable reliability was found for all measures of physical activity (PA) overall and across different types of neighborhood. Participants from highly walkable neighborhoods were more reliable at estimating walking for transport. Participants from low-SES areas were less reliable at estimating leisure-time PA and sitting but more reliable at estimating transport-related walking. IPAQ-LC walking was significantly related to light- but not moderate-intensity accelerometry-based PA. It was moderately to strongly related to a 7-day diary of walking. The data imply slow-paced walking, probably due to age, climate, and terrain. The findings suggest that the IPAQ-LC’s reliability and validity are acceptable in Chinese seniors

Low-salinity transitions drive abrupt microbial response to sea-level change

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Authors have data permissions for all data used in this study. Data deriving from published sources are referenced in the manuscript. The datasets used in this study are available from the British Antarctic Survey Polar Data Centre, and the figshare repository (https://doi.org/10.6084/m9.figshare.16573346.v1).The salinisation of many coastal ecosystems is underway and is expected to continue into the future because of sea-level rise and storm intensification brought about by the changing climate. However, the response of soil microbes to increasing salinity conditions within coastal environments is poorly understood, despite their importance for nutrient cascading, carbon sequestration and wider ecosystem functioning. Here, we demonstrate deterioration in the productivity of a top-tier microbial group (testate amoebae) with increasing coastal salinity, which we show to be consistent across phylogenetic groups, salinity gradients, environment types and latitude. Our results show that microbial changes occur in the very early stages of marine inundation, presaging more radical changes in soil and ecosystem function and providing an early warning of coastal salinisation that could be used to improve coastal planning and adaptation.Natural Environment Research Council (NERC)Sécurité publique du QuébecUniversity of Exete

P19-23. Putative prefusion mechanism of HIV-1 Env revealed by ligand-induced quaternary alterations in o-gp140 trimers

International audienc

Associations between Traffic-Related Air Pollution and Cognitive Function in Australian Urban Settings: The Moderating Role of Diabetes Status

Traffic-related air pollution (TRAP) is associated with lower cognitive function and diabetes in older adults, but little is known about whether diabetes status moderates the impact of TRAP on older adult cognitive function. We analysed cross-sectional data from 4141 adults who participated in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study in 2011–2012. TRAP exposure was estimated using major and minor road density within multiple residential buffers. Cognitive function was assessed with validated psychometric scales, including: California Verbal Learning Test (memory) and Symbol–Digit Modalities Test (processing speed). Diabetes status was measured using oral glucose tolerance tests. We observed positive associations of some total road density measures with memory but not processing speed. Minor road density was not associated with cognitive function, while major road density showed positive associations with memory and processing speed among larger buffers. Within a 300 m buffer, the relationship between TRAP and memory tended to be positive in controls (β = 0.005; p = 0.062), but negative in people with diabetes (β = −0.013; p = 0.026) and negatively associated with processing speed in people with diabetes only (β = −0.047; p = 0.059). Increased TRAP exposure may be positively associated with cognitive function among urban-dwelling people, but this benefit may not extend to those with diabetes

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Utility of salt-marsh foraminifera, testate amoebae and bulk-sediment δ13C values as sea-level indicators in Newfoundland, Canada

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.We investigated the utility of foraminifera, testate amoebae and bulk-sediment δ 13 C measurements for reconstructing Holocene relative sea level from sequences of salt-marsh sediment in Newfoundland, Canada. Modern, surface sediment was collected along transects from low to supra-tidal elevations in eastern (at Placentia) and western (at Hynes Brook and Big River) Newfoundland. Consistent with previous work, low-diversity assemblages of foraminifera display an almost binary division into a higher salt-marsh assemblage dominated by Jadammina macrescens and Balticammina pseudomacrescens and a lower salt-marsh assemblage comprised of Miliammina fusca. This pattern and composition resembles those identified at other high latitude sites with cool climates and confirms that foraminifera are sea-level indicators. The lowest occurrence of testate amoebae was at approximately mean higher high water. The composition of high salt-marsh testate amoebae assemblages (Centropyxis cassis type, Trinema spp., Tracheleuglypha dentata type, and Euglypha spp.) in Newfoundland was similar to elsewhere in the North Atlantic, but preservation bias favors removal of species with idiosomic tests over those with xenosomic tests. The mixed high salt-marsh plant community in Newfoundland results in bulk surface-sediment δ 13 C values that are typical of C 3 plants, making them indistinguishable from freshwater sediment. Therefore we propose that the utility of this proxy for reconstructing RSL in eastern North America is restricted to the coastline between Chesapeake Bay and southern Nova Scotia. Using a simple, multi-proxy approach to establish that samples in three radiocarbon-dated sediment cores formed between the lowest occurrence of testate amoebae and the highest occurrence of foraminifera, we generated three example late Holocene sea-level index points at Hynes Brook.This work was supported by NSF awards OCE-1458921, OCE-1458904 and EAR-1402017 and the Robert L. Nichols student research fund of the Department of Earth and Ocean Sciences at Tufts University. Foraminiferal data from Hynes Brook and Big River were collected as part of a series of projects including “Ocean-climate variability and sea level in the North Atlantic region since AD 0” funded by the Dutch National Research Programme (NRP) on Global air pollution and Climate Change; “Coastal Records” funded by the Vrije Universiteit Amsterdam and “Simulations, Observations & Palaeoclimatic data: climate variability over the last 500 years” funded by the European Union

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)