1,242 research outputs found
Improvement of Fourier Polarimetry for applications in tomographic photoelasticity
The use of the Fourier Polarimetry method has been demonstrated to extract the three characteristic parameters in integrated photoelasticity. In contrast to the phase-stepping method, it has been shown that the Fourier method is more accurate. However, the Fourier method isn't very efficient as it requires that a minimum of nine intensity images be collected during a whole revolution of a polarizer while the phase-stepping method only needs six intensity images. In this paper the Fourier transformation is used to derive the expression for determination of the characteristic parameters. Four Fourier coefficients are clearly identified to calculate the three characteristic parameters. It is found that the angular rotation ratio could be set arbitrarily. The angular rotation ratio is optimized to satisfy the requirements of efficiency and proper data accuracy, which results in data collection about three times faster than the methods suggested by previous researchers. When comparing their performance in terms of efficiency and accuracy, the simulated and experimental results show that these angular rotation ratios have the same accuracy but the optimized angular rotation ratio is significantly faster. The sensitivity to noise is also investigated and further improvement of accuracy is suggested
ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury: A longitudinal ecological study
This is the final version. Available from the publisher via the DOI in this record.Background: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. Methods and Findings: English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. Conclusion: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics. © 2013 Tomlinson et al.Cambridge Biomedical Research InstituteBritish Heart Foundatio
The accuracy of diagnostic coding for acute kidney injury in England - A single centre study
This is the final version. Available on open access from BMC via the DOI in this recordBackground: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. Methods. We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. Results: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p<0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. Conclusions: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010. © 2013 Tomlinson et al; licensee BioMed Central Ltd.Cambridge Biomedical Research InstituteBritish Heart Foundatio
Compressibility of titanosilicate melts
The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility
A review of selected research priority setting processes at national level in low and middle income countries: towards fair and legitimate priority setting
<p>Abstract</p> <p>Background</p> <p>It is estimated that more than $130 billion is invested globally into health research each year. Increasingly, there is a need to set priorities in health research investments in a fair and legitimate way, using a sound and transparent methodology. In this paper we review selected priority setting processes at national level in low and middle income countries. We outline a set of criteria to assess the process of research priority setting and use these to describe and evaluate priority setting exercises that have taken place at country level. Based on these insights, recommendations are made regarding the constituents of a good priority setting process.</p> <p>Methods</p> <p>Data were gathered from presentations at a meeting held at the World Health Organization (WHO) in 2008 and a web-based search. Based on this literature review a number of criteria were developed to evaluate the priority setting processes.</p> <p>Results</p> <p>Across the countries surveyed there was a relative lack of genuine stakeholder engagement; countries varied markedly in the extent to which the priority setting processes were documented; none of the countries surveyed had a systematic or operational appeals process for outlined priorities; and in all countries (except South Africa) the priorities that were outlined described broad disease categories rather than specific research questions.</p> <p>Conclusions</p> <p>Country level priority setting processes differed significantly in terms of the methods used. We argue that priority setting processes must have in-built mechanisms for publicizing results, effective procedures to enforce decisions as well as processes to ensure that the revision of priorities happens in practice.</p
Evolutionary Games with Affine Fitness Functions: Applications to Cancer
We analyze the dynamics of evolutionary games in which fitness is defined as
an affine function of the expected payoff and a constant contribution. The
resulting inhomogeneous replicator equation has an homogeneous equivalent with
modified payoffs. The affine terms also influence the stochastic dynamics of a
two-strategy Moran model of a finite population. We then apply the affine
fitness function in a model for tumor-normal cell interactions to determine
which are the most successful tumor strategies. In order to analyze the
dynamics of concurrent strategies within a tumor population, we extend the
model to a three-strategy game involving distinct tumor cell types as well as
normal cells. In this model, interaction with normal cells, in combination with
an increased constant fitness, is the most effective way of establishing a
population of tumor cells in normal tissue.Comment: The final publication is available at http://www.springerlink.com,
http://dx.doi.org/10.1007/s13235-011-0029-
Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests
Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera
The complexities of breast cancer desmoplasia
The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas
Affinity purification of fibrinogen using an Affimer column
Background
Fibrinogen is an abundant plasma protein with an essential role in blood coagulation and haemostasis thus receiving significant research interest. However, protein purification is time consuming and commercial preparations often have protein contaminants. The aim of this study was to develop a new method to purify high quality and functional fibrinogen.
Methods
Fibrinogen-specific Affimer protein, isolated using phage display systems, was immobilised to SulfoLink resin column and employed for fibrinogen purification from plasma samples. Fibrinogen was eluted using a high pH solution. Commercial human fibrinogen was also further purified using the Affimer column. Fibrinogen purity was determined by SDS-PAGE and mass spectrometry, while functionality was assessed using turbidimetric analysis.
Results
Affimer-purified fibrinogen from human plasma showed purity at least comparable to commercially available preparations and was able to form physiological fibrin networks. Further purification of commercially available fibrinogen using the Affimercolumn eliminated multiple contaminant proteins, a significant number of which are key elements of the coagulation cascade, including plasminogen and factor XIII.
Conclusions
The Affimercolumn represents a proof of concept novel, rapid method for isolating functional fibrinogen from plasma and for further purification of commercially available fibrinogen preparations.
General significance
Our methodology provides an efficient way of purifying functional fibrinogen with superior purity without the need of expensive pieces of equipment or the use of harsh conditions
Biology of a new virus isolated from Lupinus nootkatensis plants in Alaska
A new virus named Nootka lupine vein-clearing virus (NLVCV) was isolated from Lupinus nootkatensis plants that were confined to a relatively small area in the Talkeetna mountains of south-central Alaska. Annual surveys (2000–03) consistently found leaf symptoms of pronounced vein clearing and mosaic on 3- to 4-week-old plants in late June. Spherical particles ≈ 30 nm in diameter were isolated from these leaves. Virions contained a single-stranded RNA of ≈ 4·0–4·2 kb and one species of capsid protein estimated to be ≈ 40 kDa. The double-stranded RNA profile from naturally infected leaves consisted of three major bands ≈ 4·2, 1·9 and 1·5 kbp. Protein extractions from either sap or virions of diseased plants reacted to polyclonal antiserum made against the virions in Western blot assays. A predicted PCR product ≈ 500 bp was synthesized from virion RNA using primers specific to the carmovirus RNA-dependent RNA polymerase (RDRP) gene. The nucleotide sequence of the amplified DNA did not match any known virus, but contained short regions of identity to several carmoviruses. Only species belonging to the Fabaceae were susceptible to NLVCV by mechanical inoculation. Based on dsRNA profile, size of virion RNA genome and capsid protein, and similarity of the RDRP gene to that of other carmoviruses, it is suggested that NLVCV is a member of the family Tombusviridae , and tentatively of the genus Carmovirus . As the host range, RDRP gene and dsRNA profile of NLVCV are different from those of known viruses, this is a newly described plant virus
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