Angina at Low heart rate And Risk of imminent Myocardial infarction (the ALARM study): a prospective, observational proof-of-concept study

BACKGROUND: Myocardial infarction (MI) is often preceded by unstable angina. Helping patients identify the onset of unstable angina rather than MI may result in earlier treatment and improve outcomes. Unstable angina is angina occurring at a lower-than-usual workload. Since heart rate (HR) is correlated with degree of exertion, we hypothesised that angina occurring at low HR is a warning signal for unstable angina and MI. METHODS: In this prospective study, 111 patients with acute coronary syndrome (ACS) or prognostically significant coronary disease were recruited. Each patient’s HR was measured using a portable electrocardiogram (ECG) recorder after regular class III exercise on the Canadian Cardiovascular Society Angina Grading Scale and the cumulative moving average and three-sigma (standard deviation) range were calculated for each new measurement. The HR was subsequently measured at the beginning of angina; a HR lower than the preceding three-sigma ranges for class III or anginal HR was regarded as a ‘warning signal’. The proportion of warning signals associated with ACS occurring in the following 2 weeks was compared with that for non-warning signals. RESULTS: Nine cases of ACS occurred in eight patients. Two cases were preceded by warning signals; a signal marked the onset of ACS in a third patient, and four patients failed to make anginal ECG recordings. There were 591 documented episodes of angina during the study and ECGs were available for 383 (64.8 %) of these of which 55 were warning signals. Of these warning signals, 4 occurred in the 2 weeks preceding ACS, compared with 4 of 328 non-warning signals (odds ratio, 6.4; 95 % confidence interval, 1.5–26.2; p = 0.01; positive predictive value, 7.3 %; negative predictive value, 98.8 %). CONCLUSIONS: Low HR angina may identify unstable angina and serve as an early warning for MI. In addition, angina that does not occur at a low heart rate indicates that ACS is very unlikely

Pii‐21

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109873/1/cptclpt2006159.pd

Palaeobiology, ecology, and distribution of stromatoporoid faunas in biostromes of the mid-Ludlow of Gotland

Six well exposed mid−Ludlow stromatoporoid−dominated reef biostromes in four localities from the Hemse Group in southeastern Gotland, Sweden comprise a stromatoporoid assemblage dominated by four species; Clathrodictyon mohicanum, “Stromatopora” bekkeri, Plectostroma scaniense, and Lophiostroma schmidtii. All biostromes investigated in this area (of approximately 30 km2) are interpreted to belong to a single faunal assemblage forming a dense accumulation of fossils that is probably the best exposed stromatoporoid−rich deposit of the Silurian. The results from this comprehensive study strengthen earlier interpretations of a combination of genetic and environmental control on growth−forms of the stromatoporoids. Growth styles are similar for stromatoporoids in all six biostromes. Differences in biostrome fabric are due to variations in the degree of disturbance by storms. The uniformity of facies and the widespread low−diversity fauna support the view that palaeoenvironmental conditions were similar across the area where these biostromes crop out, and promoted the extraordinary growth of stromatoporoids in this shallow shelf area

Changing geo-ecological functions of coral reefs in the Anthropocene

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record The ecology of many coral reefs has changed markedly over recent decades in response to various combinations of local and global stressors. These ecological changes have important implications for the abundance of taxa that regulate the production and erosion of skeletal carbonates, and thus for many of the geo-ecological functions that coral reefs provide, including reef framework production and sediment generation, the maintenance of reef habitat complexity and reef growth potential. These functional attributes underpin many of the ecosystem goods and services that reefs provide to society. Rapidly changing conditions of reefs in the Anthropocene are likely to significantly impact the capacity of reefs to sustain these geo-ecological functions. Although the Anthropocene footprint of disturbance will be expressed differently across ecoregions and habitats, the end point for many reefs may be broadly similar: (a) progressively shifting towards net neutral or negative carbonate budget states; (b) becoming structurally flatter; and (c) having lower vertical growth rates. It is also likely that a progressive depth-homogenisation will occur in terms of these processes. The Anthropocene is likely to be defined by an increasing disconnect between the ecological processes that drive carbonate production on the reef surface, and the net geological outcome of that production, that is, the accumulation of the underlying reef structure. Reef structures are thus likely to become increasingly relict or senescent features, which will reduce reef habitat complexity and sediment generation rates, and limit reef potential to accrete vertically at rates that can track rising sea levels. In the absence of pervasive stressors, recovery of degraded coral communities has been observed, resulting in high net-positive budgets being regained. However, the frequency and intensity of climate-driven bleaching events are predicted to increase over the next decades. This would increase the spatial footprint of disturbances and exacerbate the magnitude of the changes described here, limiting the capacity of many reefs to maintain their geo-ecological functions. The enforcement of effective marine protection or the benefits of geographic isolation or of favourable environmental conditions (“refugia” sites) may offer the hope of more optimistic futures in some locations. A plain language summary is available for this article.Royal Societ

Extreme spatial heterogeneity in carbonate accretion potential on a Caribbean fringing reef linked to local human disturbance gradients

This is the final version. Available on open access from Wiley via the DOI in this recordThe capacity of coral reefs to maintain their structurally complex frameworks and to retain the potential for vertical accretion is vitally important to the persistence of their ecological functioning and the ecosystem services they sustain. However, datasets to support detailed along-coast assessments of framework production rates and accretion potential do not presently exist. Here we estimate, based on gross bioaccretion and bioerosion measures, the carbonate budgets and resultant maximum accretion potential (RAPmax) of the shallow reef zone of leeward Bonaire – between 5 to 12 m depth – at unique fine spatial resolution along this coast (115 sites). Whilst the fringing reef of Bonaire is often reported to be in a better ecological condition than most sites throughout the wider Caribbean region, our data show that the carbonate budgets of the reefs and derived RAPmax rates varied3 considerably across this ~58 km long fringing reef complex. Some areas, in particular the marine reserves, were indeed still dominated by structurally complex coral communities with high net carbonate production (> 10 kg CaCO3 m-2 year-1 35 ), high live coral cover and complex structural topography. The majority of the studied sites, however, were defined by relatively low budget states (< 2 kg CaCO3 m-2 year-1 36 ) or were in a state of net erosion. These data highlight the marked spatial heterogeneity that can occur in budgets states, and thus in reef accretion potential, even between quite closely spaced areas of individual reef complexes. This heterogeneity is linked strongly to the degree of localized land-based impacts along the coast, and resultant differences in the abundance of reef framework building coral species. The major impact of this variability is that those sections of reef defined by low-accretion potential will have limited capacity to maintain their structural integrity and to keep pace with current projections of climate change induced sea-level rise (SLR), thus posing a threat to reef functioning, biodiversity and trophic cascades. Since many Caribbean reefs are more severely degraded than those found around Bonaire, it is to be expected that the findings presented here are rather the rule than the exception, but the study also highlights the need for similar high spatial resolution (along-coast) assessments of budget states and accretion potential to meaningfully explore increasing coastal risk at the country level. The findings also more generally underline the significance of reducing local anthropogenic disturbance and restoring framework-building coral assemblages. Appropriately focussed local preservation efforts may aid in averting future large-scale submergence of Caribbean coral reefs and will constrain the social and economic implications associated with the loss of reef goods and services.Ministry of Economic AffairsWageningen UniversityRoyal Netherlands Institute for Sea Researc

Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre.

OBJECTIVE: To investigate the clinical and pathological trends, over a 10-year period, in robot-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. PATIENTS AND METHODS: In all, 1 500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data were collected on clinicopathological details at presentation as well as surgical outcomes and compared over time. RESULTS: The median (range) age of patients throughout the period was 62 (35-78) years. The proportion of preoperative high-grade cases (Gleason score 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (P < 0.001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (P < 0.001). The median prostate-specific antigen (PSA) level at diagnosis did not alter significantly. Overall, 11.6% of men in 2005-2008 were classified preoperatively as high-risk by National Institute for Health and Care Excellence criteria, compared with 33.6% in 2013-2015 (P < 0.001). The corresponding proportions for low-risk cases were 48.6% and 17.3%, respectively. Final surgical pathology showed an increase in tumour stage, Gleason grade, and nodal status over time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-2015 (P < 0.001), Gleason score 9-10 tumours increased from 1.8% to 9.1% (P < 0.001) and positive nodal status increased from 1.6% to 12.9% (P < 0.001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (P = 0.72). CONCLUSION: This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher stage and more advanced disease being referred and operated on. However, surgical margin outcomes have remained good.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bju.1351

The taxonomic name resolution service : an online tool for automated standardization of plant names

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Bioinformatics 14 (2013): 16, doi:10.1186/1471-2105-14-16.The digitization of biodiversity data is leading to the widespread application of taxon names that are superfluous, ambiguous or incorrect, resulting in mismatched records and inflated species numbers. The ultimate consequences of misspelled names and bad taxonomy are erroneous scientific conclusions and faulty policy decisions. The lack of tools for correcting this ‘names problem’ has become a fundamental obstacle to integrating disparate data sources and advancing the progress of biodiversity science. The TNRS, or Taxonomic Name Resolution Service, is an online application for automated and user-supervised standardization of plant scientific names. The TNRS builds upon and extends existing open-source applications for name parsing and fuzzy matching. Names are standardized against multiple reference taxonomies, including the Missouri Botanical Garden's Tropicos database. Capable of processing thousands of names in a single operation, the TNRS parses and corrects misspelled names and authorities, standardizes variant spellings, and converts nomenclatural synonyms to accepted names. Family names can be included to increase match accuracy and resolve many types of homonyms. Partial matching of higher taxa combined with extraction of annotations, accession numbers and morphospecies allows the TNRS to standardize taxonomy across a broad range of active and legacy datasets. We show how the TNRS can resolve many forms of taxonomic semantic heterogeneity, correct spelling errors and eliminate spurious names. As a result, the TNRS can aid the integration of disparate biological datasets. Although the TNRS was developed to aid in standardizing plant names, its underlying algorithms and design can be extended to all organisms and nomenclatural codes. The TNRS is accessible via a web interface at http://tnrs.iplantcollaborative.org/ webcite and as a RESTful web service and application programming interface. Source code is available at https://github.com/iPlantCollaborativeOpenSource/TNRS/ webcite.BJE was supported by NSF grant DBI 0850373 and TR by CSIRO Marine and Atmospheric Research, Australia,. BB and BJE acknowledge early financial support from Conservation International and TEAM who funded the development of early prototypes of taxonomic name resolution. The iPlant Collaborative (http://www.iplantcollaborative.org) is funded by a grant from the National Science Foundation (#DBI-0735191)

The karyotype of Nothoscordum arenarium Herter (Gilliesioideae, Alliaceae): A populational and cytomolecular analysis

The genus Nothoscordum Kunth comprises approximately 20 species native to South America. Karyologically, the genus is remarkable for its large chromosomes and Robertsonian translocations. Variation in chromosome number has been recorded in a few polyploid species and it is unknown among diploids. This study presents the chromosome number and morphology of 53 individuals of seven populations of N. arenarium Herter (2n = 10). In addition, karyotype analyses after C-banding, staining with CMA and DAPI, and in situ hybridization with 5S and 45S rDNA probes were performed in six individuals from one population. All individuals exhibited 2n = 10 (6M + 4A), except for one tetraploid (2n = 20, 12M + 8A) and one triploid (2n = 15, 9M + 6A) plant. C-banding revealed the presence of CMA+ /DAPI - heterochromatin in the short arm and in the proximal region of the long arm of all acrocentric chromosomes. The 45S rDNA sites co-localized with the CMA + regions of the acrocentrics short arms, while the 5S rDNA probe only hybridized with the subterminal region of a pair of metacentric chromosomes. A change in the pattern of CMA bands and rDNA sites was observed in only one individual bearing a reciprocal translocation involving the long arm of a metacentric and the long arm of an acrocentric chromosome. These data suggest that, despite isolated cases of polyploidy and translocation, the karyotype of N. arenarium is very stable and the karyotypic instability described for other species may be associated with their polyploid condition

Caribbean-wide decline in carbonate production threatens coral reef growth

This a post-print, author-produced version of an article accepted for publication in Nature Communications. Copyright © 2013 Nature Publishing Group . The definitive version is available at http://www.nature.com/ncomms/journal/v4/n1/full/ncomms2409.htmlGlobal-scale deteriorations in coral reef health have caused major shifts in species composition. One projected consequence is a lowering of reef carbonate production rates, potentially impairing reef growth, compromising ecosystem functionality and ultimately leading to net reef erosion. Here, using measures of gross and net carbonate production and erosion from 19 Caribbean reefs, we show that contemporary carbonate production rates are now substantially below historical (mid- to late-Holocene) values. On average, current production rates are reduced by at least 50%, and 37% of surveyed sites were net erosional. Calculated accretion rates (mm year(-1)) for shallow fore-reef habitats are also close to an order of magnitude lower than Holocene averages. A live coral cover threshold of ~10% appears critical to maintaining positive production states. Below this ecological threshold carbonate budgets typically become net negative and threaten reef accretion. Collectively, these data suggest that recent ecological declines are now suppressing Caribbean reef growth potential

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Cambridge work was funded by a CRUK programme grant awarded to DEN; Swedish work and tissue collections were funded by grants from the Linne Centre for Breast and Prostate Cancer (CRISP, grant 70867901), Karolinska Institutet, the Swedish Research Council (K2010-70X-20430-04-3), and the Swedish Cancer Society (11-0287).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2015.07.01