The process of EDC-NHS Cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment.

We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy (AFM) and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres.The authors would like to acknowledge the support of the Engineering and Physical Sciences Research Council (EPSRC), UK through a Knowledge Transfer Secondment (KTS) (to JHS), The National Institute for Health Research (NIHR) through their i4i grant to Tigenix Ltd and the TSB grant TP/8/BIO/6/I/Q0052.This is the accepted manuscript. The final version is available from AIP at http://scitation.aip.org/content/aip/journal/aplmater/3/1/10.1063/1.4900887

The use of kurtosis de-noising for EEG analysis of patients suffering from Alzheimer's disease.

The use of electroencephalograms (EEGs) to diagnose and analyses Alzheimer’s disease (AD) has received much attention in recent years. The sample entropy (SE) has been widely applied to the diagnosis of AD. In our study, nine EEGs from 21 scalp electrodes in 3 AD patients and 9 EEGs from 3 age-matched controls are recorded. The calculations show that the kurtoses of the AD patients’ EEG are positive and much higher than that of the controls. This finding encourages us to introduce a kurtosis-based de-noising method. The 21-electrode EEG is first decomposed using independent component analysis (ICA), and second sort them using their kurtoses in ascending order. Finally, the subspace of EEG signal using back projection of only the last five components is reconstructed. SE will be calculated after the above de-noising preprocess. The classifications show that this method can significantly improve the accuracy of SE-based diagnosis. The kurtosis analysis of EEG may contribute to increasing the understanding of brain dysfunction in AD in a statistical way

Effect of fiber crosslinking on collagen-fiber reinforced collagen-chondroitin-6-sulfate materials for regenerating load-bearing soft tissues.

Porous collagen-glycosaminoglycan structures are bioactive and exhibit a pore architecture favorable for both cellular infiltration and attachment; however, their inferior mechanical properties limit use, particularly in load-bearing situations. Reinforcement with collagen fibers may be a feasible route for enhancing the mechanical characteristics of these materials, providing potential for composites used for the repair and regeneration of soft tissue such as tendon, ligaments, and cartilage. Therefore, this study investigates the reinforcement of collagen-chondroitin-6-sulfate (C6S) porous structures with bundles of extruded, reconstituted type I collagen fibers. Fiber bundles were produced through extrusion and then, where applicable, crosslinked using a solution of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide. Fibers were then submerged in the collagen-C6S matrix slurry before being lyophilized. A second 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide crosslinking process was then applied to the composite material before a secondary lyophilization cycle. Where bundles had been previously crosslinked, composites withstood a load of approximately 60 N before failure, the reinforcing fibers remained dense and a favorable matrix pore structure resulted, with good interaction between fiber and matrix. Fibers that had not been crosslinked before lyophilization showed significant internal porosity and a channel existed between them and the matrix. Mechanical properties were significantly reduced, but the additional porosity could prove favorable for cell migration and has potential for directing aligned tissue growth.This is the pre-peer reviewed version of the following article: J.H. Shepherd, S. Ghose, A. Moavenian, S.J. Kew, S.M. Best and R.E. Cameron. “Effect of fibre Cross-linking on Collagen-fibre reinforced Collagen-chondroitin-6-sulphate materials for regenerating load-bearing soft tissues”. Journal of Biomedical Materials Research: Part A, 2013;101(1):176-84., which has been published in final form at http://dx.doi.org/10.1002/jbm.a.34317

A novel application of PageRank and user preference algorithms for assessing the relative performance of track athletes in competition

Ranking enables coaches, sporting authorities, and pundits to determine the relative performance of individual athletes and teams in comparison to their peers. While ranking is relatively straightforward in sports that employ traditional leagues, it is more difficult in sports where competition is fragmented (e.g. athletics, boxing, etc.), with not all competitors competing against each other. In such situations, complex points systems are often employed to rank athletes. However, these systems have the inherent weakness that they frequently rely on subjective assessments in order to gauge the calibre of the competitors involved. Here we show how two Internet derived algorithms, the PageRank (PR) and user preference (UP) algorithms, when utilised with a simple ‘who beat who’ matrix, can be used to accurately rank track athletes, avoiding the need for subjective assessment. We applied the PR and UP algorithms to the 2015 IAAF Diamond League men’s 100m competition and compared their performance with the Keener, Colley and Massey ranking algorithms. The top five places computed by the PR and UP algorithms, and the Diamond League ‘2016’ points system were all identical, with the Kendall’s tau distance between the PR standings and ‘2016’ points system standings being just 15, indicating that only 5.9% of pairs differed in their order between these two lists. By comparison, the UP and ‘2016’ standings displayed a less strong relationship, with a tau distance of 95, indicating that 37.6% of the pairs differed in their order. When compared with the standings produced using the Keener, Colley and Massey algorithms, the PR standings appeared to be closest to the Keener standings (tau distance = 67, 26.5% pair order disagreement), whereas the UP standings were more similar to the Colley and Massey standings, with the tau distances between these ranking lists being only 48 (19.0% pair order disagreement) and 59 (23.3% pair order disagreement) respectively. In particular, the UP algorithm ranked ‘one-off’ victors more highly than the PR algorithm, suggesting that the UP algorithm captures alternative characteristics to the PR algorithm, which may more suitable for predicting future performance in say knockout tournaments, rather than for use in competitions such as the Diamond League. As such, these Internet derived algorithms appear to have considerable potential for objectively assessing the relative performance of track athletes, without the need for complicated points equivalence tables. Importantly, because both algorithms utilise a ‘who beat who’ model, they automatically adjust for the strength of the competition, thus avoiding the need for subjective decision making

Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow.

To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging.Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled ≥2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes.CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021).CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Thermal energy transfer around buried pipe infrastructure

Decarbonisation of heating is essential to meet national and international greenhouse gas emissions targets. This will require adoption of a range of solutions including ground source heat pump and district heating technologies. A novel route to these solutions includes dual use of buried infrastructure for heat transfer and storage in addition to its primary function. Water supply and wastewater collection pipes may be well suited for thermal energy applications being present in all urban areas in networks already in proximity to heat users. However, greater understanding of their potential interactions with surrounding heat sources and sinks is required before full assessment of the energy potential of such buried pipe networks can be obtained. This paper presents an investigation into the thermal interactions associated with shallow, buried water filled pipes. Using the results of large scale experiments and numerical simulation it is shown that soil surface ambient conditions and adjacent pipes can both act as sources or sinks of heat. While conduction is the main mechanism of heat transfer in the soil directly surrounding any pipe, any adjacent water filled pipes may lead to convection becoming important locally. In the test case, the thermal sphere of influence of the water filled pipe was also shown to be large, at in excess of 4 m over a timescale of 4 months. Taken together, these points suggest that design and analysis approaches when using water supply and wastewater collection networks for heat exchange and storage need careful consideration of environmental interactions, heat losses and gains to adjacent pipes or other infrastructure, and in ground conditions for a number of pipe diameters from any buried pipe

Yours ever (well, maybe): Studies and signposts in letter writing

Electronic mail and other digital communications technologies seemingly threaten to end the era of handwritten and typed letters, now affectionately seen as part of snail mail. In this essay, I analyze a group of popular and scholarly studies about letter writing-including examples of pundits critiquing the use of e-mail, etiquette manuals advising why the handwritten letter still possesses value, historians and literary scholars studying the role of letters in the past and what it tells us about our present attitudes about digital communications technologies, and futurists predicting how we will function as personal archivists maintaining every document including e-mail. These are useful guideposts for archivists, providing both a sense of the present and the past in the role, value and nature of letters and their successors. They also provide insights into how such documents should be studied, expanding our gaze beyond the particular letters, to the tools used to create them and the traditions dictating their form and function. We also can discern a role for archivists, both for contributing to the literature about documents and in using these studies and commentaries, suggesting not a new disciplinary realm but opportunities for new interdisciplinary work. Examining a documentary form makes us more sensitive to both the innovations and traditions as it shifts from the analog to the digital; we can learn not to be caught up in hysteria or nostalgia about one form over another and archivists can learn about what they might expect in their labors to document society and its institutions. At one time, paper was part of an innovative technology, with roles very similar to the Internet and e-mail today. It may be that the shifts are far less revolutionary than is often assumed. Reading such works also suggests, finally, that archivists ought to rethink how they view their own knowledge and how it is constructed and used. © 2010 Springer Science+Business Media B.V

A disk of dust and molecular gas around a high-mass protostar

The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (> 8 x Sun's mass) stars has heretofore remained poorly understood. Recent observational studies suggest that high-mass stars may form in essentially the same way as low-mass stars, namely via an accretion process, instead of via merging of several low-mass (< 8 Msun) stars. However, there is as yet no conclusive evidence. Here, we report the discovery of a flattened disk-like structure observed at submillimeter wavelengths, centered on a massive 15 Msun protostar in the Cepheus-A region. The disk, with a radius of about 330 astronomical units (AU) and a mass of 1 to 8 Msun, is detected in dust continuum as well as in molecular line emission. Its perpendicular orientation to, and spatial coincidence with the central embedded powerful bipolar radio jet, provides the best evidence yet that massive stars form via disk accretion in direct analogy to the formation of low-mass stars