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Reactivation of Kamb Ice Stream tributaries triggers century-scale reorganization of Siple Coast ice flow in West Antarctica
Ongoing, centennial-scale flow variability within the Ross ice streams of West Antarctica suggests that the present-day positive mass balance in this region may reverse in the future. Here, we use a three-dimensional ice-sheet model to simulate ice flow in this region over 250 years. The flow responds to changing basal properties, as a subglacial till layer interacts with water transported in an active subglacial hydrological system. We show that a persistent weak bed beneath the tributaries of the dormant Kamb Ice Stream is a source of internal ice-flow instability, which reorganizes all ice streams in this region, leading to a reduced (positive) mass balance within decades and a net loss of ice within two centuries. This hitherto unaccounted for flow variability could raise sea-level by 5mm this century. Better constraints on future sea-level change from this region will require improved estimates of geothermal heat flux and subglacial water transport.This work was carried out with support from the Isaac Newton trust, Cecil H. and Ida M. Green Foundation and Natural Environment Research Council (grants NE/E005950/1 and NE/J005800/1). SFP was supported by the U.S. Department of Energy Office of Science, Biological and Environmental Research program. ST acknowledges support from National Science Foundation (grant #0338295). SPC was supported by funding from the Cryospheric Sciences program of NASA and HAF was supported by funding from NSF (grant ANT-0838885 (Fricker)). The source code for the results presented can be obtained by contacting the corresponding author directlyThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/2015GL06578
Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers
Aim
To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs).
Background
Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial.
Methods
A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model.
Results
Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings.
Conclusion
The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs
Syntactic discriminative language model rerankers for statistical machine translation
This article describes a method that successfully exploits syntactic features for n-best translation candidate reranking using perceptrons. We motivate the utility of syntax by demonstrating the superior performance of parsers over n-gram language models in differentiating between Statistical Machine Translation output and human translations. Our approach uses discriminative language modelling to rerank the n-best translations generated by a statistical machine translation system. The performance is evaluated for Arabic-to-English translation using NIST’s MT-Eval benchmarks. While deep features extracted from parse trees do not consistently help, we show how features extracted from a shallow Part-of-Speech annotation layer outperform a competitive baseline and a state-of-the-art comparative reranking approach, leading to significant BLEU improvements on three different test sets
Rehabilitation for post-stroke cognitive impairment: an overview of recommendations arising from systematic reviews of current evidence
Increased entropy of signal transduction in the cancer metastasis phenotype
Studies into the statistical properties of biological networks have led to
important biological insights, such as the presence of hubs and hierarchical
modularity. There is also a growing interest in studying the statistical
properties of networks in the context of cancer genomics. However, relatively
little is known as to what network features differ between the cancer and
normal cell physiologies, or between different cancer cell phenotypes. Based on
the observation that frequent genomic alterations underlie a more aggressive
cancer phenotype, we asked if such an effect could be detectable as an increase
in the randomness of local gene expression patterns. Using a breast cancer gene
expression data set and a model network of protein interactions we derive
constrained weighted networks defined by a stochastic information flux matrix
reflecting expression correlations between interacting proteins. Based on this
stochastic matrix we propose and compute an entropy measure that quantifies the
degree of randomness in the local pattern of information flux around single
genes. By comparing the local entropies in the non-metastatic versus metastatic
breast cancer networks, we here show that breast cancers that metastasize are
characterised by a small yet significant increase in the degree of randomness
of local expression patterns. We validate this result in three additional
breast cancer expression data sets and demonstrate that local entropy better
characterises the metastatic phenotype than other non-entropy based measures.
We show that increases in entropy can be used to identify genes and signalling
pathways implicated in breast cancer metastasis. Further exploration of such
integrated cancer expression and protein interaction networks will therefore be
a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table
A telephone survey of cancer awareness among frontline staff: informing training needs
Background:
Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff.
Methods:
A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England.
Results:
A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276).
Conclusion:
Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors
Exploiting inflammation for therapeutic gain in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC
Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients
Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung
Relevance of biomarkers across different neurodegenerative
Background: The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is
growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use,
appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in
strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For
example, neuropathological investigations of Alzheimer’s disease pathogenesis can fall in disagreement with conclusions
reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research
methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field.
Purpose of review: Along with separate review articles covering fluid and imaging biomarkers in this issue of Alzheimer’s
Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases
course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease
research, commenting on appropriate use, interpretation, and considerations for implementation across different
neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other
disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel
modalities that have been proposed in the landscape of neurodegenerative disease research and care
Measurement of triple gauge boson couplings from W⁺W⁻ production at LEP energies up to 189 GeV
A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb⁻¹. After combining with our previous measurements at centre-of-mass energies of 161–183 GeV we obtain κ = 0.97_{-0.16}^{+0.20}, g_{1}^{z} = 0.991_{-0.057}^{+0.060} and λ = -0.110_{-0.055}^{+0.058}, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their Standard Model values. These results are consistent with the Standard Model expectations
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