3-D magnetic resonance angiography versus conventional angiography in peripheral arterial disease: Pilot study

Angiography is usually performed as the preoperative road map for those requiring revascularization for lower extremity peripheral arterial disease (PAD). The alternative investigations are ultrasound, 3-D magnetic resonance angiography (3-D MRA) and computed tomography angiography. This pilot study aimed to assess whether 3-D MRA could replace the gold standard angiography in preoperative planning. Eight patients considered for aortoiliac or infrainguinal arterial bypass surgery were recruited. All underwent both imaging modalities within 7 days. A vascular surgeon and a radiologist each reported on the images from both the 3-D MRA and the angiography, with blinding to patient details and each others reports. Comparisons were made between the reports for the angiographic and the 3-D MRA images, and between the reports of the vascular surgeon and the radiologist. Compared to the gold standard angiogram, 3-D MRA had a sensitivity of 77% and specificity of 94% in detecting occlusion, and a sensitivity of 72% and specificity of 90% in differentiating high grade (> 50%) versus low grade (< 50%) stenoses. There was an overall concordance of 78% between the two investigations with a range of 62% in the peroneal artery to 94% in the aorta. 3-D MRA showed flow in 23% of cases where conventional angiography showed no flow. In the present pilot study, 3-D MRA had reasonable concordance with the gold standard angiography, depending on the level of the lesion. At times it showed vessel flow where occlusion was shown on conventional angiogram. 3-D MRA in peripheral vascular disease is challenging the gold standard, but is inconsistent at present.

Assessment of disease progression in motor neuron disease

Motor neuron disease (MND) is characterised by progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord. There is no pathognomonic test for the diagnosis of MND, and physicians rely on clinical criteria-upper and lower motor neuron signs-for diagnosis. The presentations, clinical phenotypes, and outcomes of MND are diverse and have not been combined into a marker of disease progression. No single algorithm combines the findings of functional assessments and rating scales, such as those that assess quality of life, with biological markers of disease activity and findings from imaging and neurophysiological assessments. Here, we critically appraise developments in each of these areas and discuss the potential of such measures to be included in the future assessment of disease progression in patients with MND.

Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers

The basis for the neuroprotectant effect of D-mannitol in reducing the sensory neurological disturbances seen in ciguatera poisoning, is unclear. Pacific ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was reversed by hyperosmolar 50 MM D-mannitol. However, using electron paramagnetic resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate hydroxyl free radicals at concentrations of toxin that caused profound effects on neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons revealed that both hyper- and iso-osmolar 50 MM D-mannitol prevented the membrane depolarisation and repetitive firing of action potentials induced by P-CTX-1. In addition, both hyper- and iso-osmolar 50 MM D-mannitol prevented the hyperpolarising shift in steady-state inactivation and the rise in leakage current through tetrodotoxin (TTX)-sensitive Na-v channels, as well as the increased rate of recovery from inactivation of TTX-resistant Nav channels induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition of peak TTX-sensitive and TTX-resistant I-Na amplitude by P-CTX-1. Additional experiments using hyper- and isoosmolar D-sorbitol, hyperosmolar sucrose and the free radical scavenging agents Trolox (R) and L-ascorbic acid showed that these agents, unlike D-mannitol, failed to prevent the effects of P-CTX-1 on spike electrogenesis and Na-v channel gating. These selective actions of D-mannitol indicate that it does not act purely as an osmotic agent to reduce swelling of nerves, but involves a more complex action dependent on the Nav channel subtype, possibly to alter or reduce toxin association. (c) 2005 Elsevier Ltd. All rights reserved.

Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats

Based on clues from epidemiology, low prenatal vitamin D has been proposed as a candidate risk factor for schizophrenia. Recent animal experiments have demonstrated that transient prenatal vitamin D deficiency is associated with persistent alterations in brain morphology and neurotrophin expression. In order to explore the utility of the vitamin D animal model of schizophrenia, we examined different types of learning and memory in adult rats exposed to transient prenatal vitamin D deficiency. Compared to control animals, the prenatally deplete animals had a significant impairment of latent inhibition, a feature often associated with schizophrenia. In addition, the deplete group was (a) significantly impaired on hole board habituation and (b) significantly better at maintaining previously learnt rules of brightness discrimination in a Y-chamber. In contrast, the prenatally deplete animals showed no impairment on the spatial learning task in the radial maze, nor on two-way active avoidance learning in the shuttle-box. The results indicate that transient prenatal vitamin D depletion in the rat is associated with subtle and discrete alterations in learning and memory. The behavioural phenotype associated with this animal model may provide insights into the neurobiological correlates of the cognitive impairments of schizophrenia. (c) 2005 Elsevier B.V. All rights reserved.

The effect of manipulations to target contrast on emmetropization in chick

Emmetropization is dependent on visual feedback and presumably some measure of the optical and image quality of the eye. We investigated the effect of simple alterations to image contrast on eye growth and refractive development. A 1.6 cyc/deg square-wave-grating target was located at the end of a 3.3 cm cone,, imaged by a +30 D lens and applied monocularly to the eyes of 8-day-old chicks. Eleven different contrast targets were tested: 95, 67, 47.5, 33.5, 24, 17, 12, 8.5, 4.2, 2.1, and 0%. Refractive error (RE), vitreous chamber depth (VC) and axial length (AL) varied with the contrast of the image (RE diff. F-10.86 = 12.420, p < 0.0005; VC diff. F-10.86 = 8.756, p < 0.0005; AL diff. F-10.86 = 9.240, p < 0.0005). Target contrasts 4.2% and lower produced relative myopia (4.2%: RE diff = -7.48 +/- 2.26 D, p = 0.987; 2.1%: RE diff = -7.22 +/- 2.77 D, p = 0.951) of similar amount to that observed in response to a featureless 0% contrast target (RE diff = -9.11 +/- 4.68 D). For target contrast levels 47.5% and greater isometropia was maintained (95%: RE diff = 1.83 +/- 2.78 D; 67%: RE diff = 0.14 +/- 1.84 D; 47.5% RE diff = 0.25 +/- 1.82 D). Contrasts in between produced an intermediate amount of myopia (33.5%: RE diff = -2.81 +/- 1.80 D; 24%: RE diff = -3.45 +/- 1.64 D; 17%: RE diff = -3.19 +/- 1.54 D; 12%: RE diff = -4.08 +/- 3.56 D; 8.5%: RE diff = -4.09 +/- 3.60 D). We conclude that image contrast provides important visual information for the eye growth control system or that contrast must reach a threshold value for some other emmetropization signal to function. (c) 2005 Elsevier Ltd. All rights reserved.

Empirical analysis of human capital development and economic growth in Europe

Recent discussion of the knowledge-based economy draws increasingly attention to the role that the creation and management of knowledge plays in economic development. Development of human capital, the principal mechanism for knowledge creation and management, becomes a central issue for policy-makers and practitioners at the regional, as well as national, level. Facing competition both within and across nations, regional policy-makers view human capital development as a key to strengthening the positions of their economies in the global market. Against this background, the aim of this study is to go some way towards answering the question of whether, and how, investment in education and vocational training at regional level provides these territorial units with comparative advantages. The study reviews literature in economics and economic geography on economic growth (Chapter 2). In growth model literature, human capital has gained increased recognition as a key production factor along with physical capital and labour. Although leaving technical progress as an exogenous factor, neoclassical Solow-Swan models have improved their estimates through the inclusion of human capital. In contrast, endogenous growth models place investment in research at centre stage in accounting for technical progress. As a result, they often focus upon research workers, who embody high-order human capital, as a key variable in their framework. An issue of discussion is how human capital facilitates economic growth: is it the level of its stock or its accumulation that influences the rate of growth? In addition, these economic models are criticised in economic geography literature for their failure to consider spatial aspects of economic development, and particularly for their lack of attention to tacit knowledge and urban environments that facilitate the exchange of such knowledge. Our empirical analysis of European regions (Chapter 3) shows that investment by individuals in human capital formation has distinct patterns. Those regions with a higher level of investment in tertiary education tend to have a larger concentration of information and communication technology (ICT) sectors (including provision of ICT services and manufacture of ICT devices and equipment) and research functions. Not surprisingly, regions with major metropolitan areas where higher education institutions are located show a high enrolment rate for tertiary education, suggesting a possible link to the demand from high-order corporate functions located there. Furthermore, the rate of human capital development (at the level of vocational type of upper secondary education) appears to have significant association with the level of entrepreneurship in emerging industries such as ICT-related services and ICT manufacturing, whereas such association is not found with traditional manufacturing industries. In general, a high level of investment by individuals in tertiary education is found in those regions that accommodate high-tech industries and high-order corporate functions such as research and development (R&D). These functions are supported through the urban infrastructure and public science base, facilitating exchange of tacit knowledge. They also enjoy a low unemployment rate. However, the existing stock of human and physical capital in those regions with a high level of urban infrastructure does not lead to a high rate of economic growth. Our empirical analysis demonstrates that the rate of economic growth is determined by the accumulation of human and physical capital, not by level of their existing stocks. We found no significant effects of scale that would favour those regions with a larger stock of human capital. The primary policy implication of our study is that, in order to facilitate economic growth, education and training need to supply human capital at a faster pace than simply replenishing it as it disappears from the labour market. Given the significant impact of high-order human capital (such as business R&D staff in our case study) as well as the increasingly fast pace of technological change that makes human capital obsolete, a concerted effort needs to be made to facilitate its continuous development.

Depth propagation and surface construction in 3-D vision

Motion discontinuities can signal object boundaries where few or no other cues, such as luminance, colour, or texture, are available. Hence, motion-defined contours are an ecologically important counterpart to luminance contours. We developed a novel motion-defined Gabor stimulus to investigate the nature of neural operators analysing visual motion fields in order to draw parallels with known luminance operators. Luminance-defined Gabors have been successfully used to discern the spatial-extent and spatial-frequency specificity of possible visual contour detectors. We now extend these studies into the motion domain. We define a stimulus using limited-lifetime moving dots whose velocity is described over 2-D space by a Gabor pattern surrounded by randomly moving dots. Participants were asked to determine whether the orientation of the Gabor pattern (and hence of the motion contours) was vertical or horizontal in a 2AFC task, and the proportion of correct responses was recorded. We found that with practice participants became highly proficient at this task, able in certain cases to reach 90% accuracy with only 12 limited-lifetime dots. However, for both practised and novice participants we found that the ability to detect a single boundary saturates with the size of the Gaussian envelope of the Gabor at approximately 5 deg full-width at half-height. At this optimal size we then varied spatial frequency and found the optimum was at the lowest measured spatial frequency (0.1 cycle deg-1 ) and then steadily decreased with higher spatial frequencies, suggesting that motion contour detectors may be specifically tuned to a single, isolated edge.

The value of magnetoencephalography to guide electrode implantation in epilepsy

To investigate if Magnetoencephalography (MEG) can add non-redundant information to guide implantation sites for intracranial recordings (IR). The contribution of MEG to intracranial recording planning was evaluated in 12 consecutive patients assessed pre-surgically with MEG followed by IR. Primary outcome measures were the identification of focal seizure onset in IR and favorable surgical outcome. Outcome measures were compared to those of 12 patients matched for implantation type in whom non-invasive pre-surgical assessment suggested clear hypotheses for implantation (non-MEG group). In the MEG group, non-invasive assessment without MEG was inconclusive, and MEG was then used to further help identify implantation sites. In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. No differences in outcome measures were found between non-MEG and MEG groups. Although the MEG group included more complex patients, it showed similar percentage of successful implantations as the non-MEG group. This suggests that MEG can contribute to identify implantation sites where standard methods failed. © 2013 Springer Science+Business Media New York.

Issues in learning an ontology from text

Ontology construction for any domain is a labour intensive and complex process. Any methodology that can reduce the cost and increase efficiency has the potential to make a major impact in the life sciences. This paper describes an experiment in ontology construction from text for the animal behaviour domain. Our objective was to see how much could be done in a simple and relatively rapid manner using a corpus of journal papers. We used a sequence of pre-existing text processing steps, and here describe the different choices made to clean the input, to derive a set of terms and to structure those terms in a number of hierarchies. We describe some of the challenges, especially that of focusing the ontology appropriately given a starting point of a heterogeneous corpus. Results - Using mainly automated techniques, we were able to construct an 18055 term ontology-like structure with 73% recall of animal behaviour terms, but a precision of only 26%. We were able to clean unwanted terms from the nascent ontology using lexico-syntactic patterns that tested the validity of term inclusion within the ontology. We used the same technique to test for subsumption relationships between the remaining terms to add structure to the initially broad and shallow structure we generated. All outputs are available at http://thirlmere.aston.ac.uk/~kiffer/animalbehaviour/ webcite. Conclusion - We present a systematic method for the initial steps of ontology or structured vocabulary construction for scientific domains that requires limited human effort and can make a contribution both to ontology learning and maintenance. The method is useful both for the exploration of a scientific domain and as a stepping stone towards formally rigourous ontologies. The filtering of recognised terms from a heterogeneous corpus to focus upon those that are the topic of the ontology is identified to be one of the main challenges for research in ontology learning.

To what extent and in what manner do Chinese and Indian contract research organisation learn and upgrade with the unbundling the global pharmaceutical R&D value chain?

The paper applies the GVC framework to analyse the organisational and geographical reconfiguration of the global R&D function of leading US and European pharmaceutical MNCs. Though pharmaceutical MNCs have been outsourcing clinical trial activities since the mid-1990s, the outsourcing of discovery research tasks is a phenomenon of the 2000s (Ramirez 2013). Moreover, in the context of a crisis of R&D productivity and increasing pressure from shareholders, a number of US and European pharmaceutical MNCs are breaking up their R&D function in an attempt to increase flexibility and reduce risk as well as costs and are thereby restructuring the global architecture of their R&D function. This break-up, or unbundling (Sako 2006), of the R&D function is particularly interesting given the prevalence of market failure in innovation (Howells et al 2008), the non-modular nature of the R&D process in this industry (Pisano 2006) and the strategic important of this activity to the core competence and long-term competitive advantage of firms in this sector. The focus of this paper is on the outsourcing of R&D activities to Chinese and Indian independently-owned contract research organisations (CROs) and the way these firms are becoming integrated as service providers into the global R&D function (or R&D value chain) of pharmaceutical MNCs. Above all the paper is concerned with the development of capabilities of CROs from these two countries and the dynamics of upgrading in GVCs in knowledge-intensive functions. The paper therefore discusses the role of both knowledge flows within global pharmaceutical R&D value chains as well as national innovation systems on the development of capabilities of Chinese and Indian CROs. Our analysis is based on data from semi-structured interviews collected from senior R&D managers from a sample of ten US and European pharmaceutical MNCs and owners and senior R&D managers from five Chinese and five Indian CROs who are providing research services to MNCs in this industry. We discuss the emergence of R&D outsourcing in this industry and the nature and mechanisms of knowledge flows within R&D value chains. The embeddedness of CROS in the national innovation systems of their home countries is also discussed.

Géniuszok párharca. Milton Friedman és J. M. Keynes vitája Tim Congdon és Robert Skidelsky előadásában = War of the geniuses. The debate between Milton Friedman and J. M. Keynes as presented by Tim Congdon and Robert Skidelsky

Tavaly ünnepelte a közgazdász-társadalom Milton Friedman Nobel-díjas közgazdász születésének századik évfordulóját. A jubileumi megemlékezésnek különös aktualitást ad, hogy a 2008 óta tartó pénzügyi világválság hátterében ismét fellobbant a 20. századi közgazdaságtan két meghatározó irányzata - a Friedman nevével fémjelzett monetarizmus és a Keynes és követői által követett keynesizmus - közötti vita. E szerteágazó vitasorozat egyik "gyöngyszeme" két nemzetközileg ismert és elismert közgazdász, Tim Congdon és Robert (Lord) Skidelsky, összecsapása a Standpoint hasábjain 2009-ben. A szerző megmutatja, hogy a vita valójában nem a pénz fontosságáról vagy a mennyiségi pénzelmélet igazságáról folyt, hanem egyrészt egy sokkal elvontabb fogalomról: a bizonytalanság közgazdasági szerepéről, másrészt gyakorlati, gazdaságpolitikai kérdésekről: a monetáris és a fiskális politika lehetséges hatékonyságáról. A máig is tartó vitában "az inga többször kilengett", hol a keynesiánusok, hol a monetaristák javára, de még semmi nem dőlt el. ____ Last year economists marked the centenary of the birth of genius among them, Milton Friedman. The commemoration was especially topical because the world financial crisis that erupted in 2008 has brought sharply into focus again the old division in 20th-century economics between monetarism and Keynesianism. One highlight in this series of disputes was the 2009 clash between two internationally known and appreciated economists Tim Congdon and Robert (Lord) Skidelsky in the columns of Standpoint. The central element in the discussion is the role of money: what kind of economic policy to pursue, monetary or fiscal, to pull troubled economies out of crisis. The question closely resembles a decisive dilemma for Keynes in the 1930s. Though Keynes turned against some basic propositions of neoclassical economics, he never challenged the importance of money to the functioning of the economy, or the validity of the quantity theory of money. The author argues here that the issue is not about the formal category of money or demand for it, but about the far deeper economic concept of the role of uncertainty in economics. Another aspect concerns the relative efficiency of various kinds of economic policy, i. e. the strengths and weaknesses of monetary and fiscal policies.

Seasonal and spatial variation in the stable isotopic composition (δ18O and δD) of precipitation in south Florida

Precipitation data collected from five sites in south Florida indicate a strong seasonal and spatial variation in δ18O and δD, despite the relatively limited geographic coverage and low-lying elevation of each of the collection sites. Based upon the weighted-mean stable isotope values, the sites were classified as coastal Atlantic, inland, and lower Florida Keys. The coastal Atlantic sites had weighted-mean values of δ18O and δD of −2.86‰ and −12.8‰, respectively, and exhibited a seasonal variation with lower δ18O and δD values in the summer wet-season precipitation (δ18O = −3.38‰, δD = −16.5‰) as compared to the winter-time precipitation (δ18O = −1.66‰, δD = −3.2‰). The inland site was characterized as having the highest d-excess value (+13.3‰), signifying a contribution of evaporated Everglades surface water to the local atmospheric moisture. In spite of its lower latitude, the lower Keys site located at Long Key had the lowest weighted-mean stable isotope values (δ18O = −3.64‰, δD = −20.2‰) as well as the lowest d-excess value of (+8.8‰). The lower δD and δ18O values observed at the Long Key site reflect the combined effects of oceanic vapor source, fractionation due to local precipitation, and slower equilibration of the larger raindrops nucleated by a maritime aerosol. Very low δ18O and δD values (δ18O < −6‰, δD < −40‰) were observed just prior to the passage of hurricanes from the Gulf of Mexico as well as during cold fronts from the north-west. These results suggest that an oceanic vapor source region to the west, may be responsible for the extremely low δD and δ18O values observed during some tropical storms and cold fronts.

Belowground decomposition of mangrove roots in Florida coastal everglades

Mangrove root decomposition rates were measured by distributing mesh bags containing fine root material across six sites with different soil fertility and hydroperiod to compare ambient differences to substrate quality. Roots from a site with lower soil phosphorus concentration were used as a reference and compared to ambient roots at five other sites with increased phosphorus concentration. Four mesh bags of each root type (ambient versus reference), separated into four 10-cm replicate intervals, were buried up to 42 cm depth at each site and incubated for 250 d (initiation in May 2004). Mass loss of ambient mangrove roots was significant at all study sites and ranged from 17% to 54%; there was no significant difference with depth at any one site. Reference decomposition constants (−k) ranged from 0.0012 to 0.0018 d−1 among Taylor Slough sites compared to 0.0023–0.0028 d−1 among Shark River sites, indicating slower decomposition rates associated with lower soil phosphorous and longer flood duration. Reference roots had similar decomposition rates as ambient roots in four of the six sites, and there were no significant correlations between indices of root substrate quality and decomposition rates. Among these distinct landscape gradients of south Florida mangroves, soil environmental conditions have a greater effect on belowground root decomposition than root substrate quality.

Vascular defects and spinal cord hypoxia in spinal muscular atrophy

© 2015 American Neurological Association. Funded by The Euan MacDonald Center for Motor Neurone Disease Research The SMA Trust Muscular Dystrophy UK The SMA Trust The SMA Trust Motor Neurone Disease Association National Institute for Health Research Great Ormond Street Hospital Biomedical Research Center Medical Research Council Great Ormond Street Hospital Charity