High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort

Aims
Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population.

Methods and results
High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events.

Conclusion
Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals.

Extremely Complex Populations of Small RNAs in the Mouse Retina and RPE/Choroid

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs of ~18-22 nucleotides in length that regulate gene expression. They are widely expressed in the retina, being both required for its normal development and perturbed in disease. The aim of this study was to apply new high-throughput sequencing techniques to more fully characterise the microRNAs and other small RNAs expressed in the retina and retinal pigment epithelium (RPE)/choroid of the mouse.

Methods: Retina and RPE/choroid were dissected from eyes of 3 month-old C57BL/6J mice. Small RNA libraries were prepared and deep sequencing performed on a Genome Analyzer (Illumina). Reads were annotated by alignment to miRBase, other non-coding RNA databases and the mouse genome.

Results: Annotation of 9 million reads to 320 microRNAs in retina and 340 in RPE/choroid provides the most comprehensive profiling of microRNAs to date. Two novel microRNAs were identified in retina. Members of the sensory organ specific miR-183,-182,-96 cluster were amongst the most highly expressed, retina-enriched microRNAs. Remarkably, microRNA 'isomiRs', which vary slightly in length and are differentially detected by Taqman RT-PCR assays, existed for all the microRNAs identified in both tissues. More variation occurred at the 3' ends, including non-templated additions of T and A. Drosha-independent mirtron microRNAs and other small RNAs derived from snoRNAs were also detected.

Conclusions: Deep sequencing has revealed the complexity of small RNA expression in the mouse retina and RPE/choroid. This knowledge will improve the design and interpretation of future functional studies of the role of microRNAs and other small RNAs in retinal disease.

Crisis Cartels:Non-Economic Values, the Public Interest and Institutional Considerations

This paper considers the use of non-economic considerations in Article 101(3) analysis of industrial restructuring agreements, using the Commission's Decisions in Synthetic Fibres, Stichting Baksteen, and the recent UK Dairy Initiative as examples. I argue that contra to the Commission's recent economics-based approach; there is room for non-economic considerations to be taken into account within the framework of the European Treaties. The competition law issue is whether the provisions of Article 101(3) can save such agreements.
I further argue that there is legal room for non-economic considerations to be considered in evaluating these restructuring agreements, it is not clear who the appropriate arbiter of these considerations should be given the institutional limitations of courts (which have no democratic mandate), specialised competition agencies (which may be too technocratic in focus) and legislatures (which are susceptible to capture by rent-seeking interest groups).

Experimental investigation of a wavelet based drive-by bridge inspection system incorporating pattern recognition

This paper presents the results of an experimental investigation, carried out in order to verify the feasibility of a ‘drive-by’ approach which uses a vehicle instrumented with accelerometers to detect and locate damage in a bridge. In theoretical simulations, a simplified vehicle-bridge interaction model is used to investigate the effectiveness of the approach in detecting damage in a bridge from vehicle accelerations. For this purpose, the accelerations are processed using a continuous wavelet transform and damage indicators are evaluated and compared. Alternative statistical pattern recognition techniques are incorporated to allow for repeated vehicle passes. Parameters such as vehicle speed, damage level, location and road roughness are varied in simulations to investigate the effect. A scaled laboratory experiment is carried out to assess the effectiveness of the approach in a more realistic environment, considering a number of bridge damage scenarios.

Monodomain strained ferroelectric PbTiO(3) thin films: Phase transition and critical thickness study

This work demonstrates that instead of paraelectric PbTiO(3), completely c-oriented ferroelectric PbTiO(3) thin films were directly grown on (001)-SrTiO(3) substrates by pulsed-laser deposition with thickness up to 340 nm at a temperature well above the Curie temperature of bulk PbTiO(3). The influence of laser-pulse frequency, substrate-surface termination on growth, and functional properties were studied using x-ray diffraction, transmission electron microscopy, and piezoresponse force microscopy. At low growth rates (frequency 8 Hz) a domains were formed for film thickness above 20-100 nm. Due to coherency strains the Curie temperature (T(c)) of the monodomain films was increased approximately by 350 degrees C with respect to the T(c) of bulk PbTiO(3) even for 280-nm-thick films. Nonetheless, up to now this type of growth mode has been considered unlikely to occur since the Matthews-Blakeslee (MB) model already predicts strain relaxation for films having a thickness of only similar to 10 nm. However, the present work disputes the applicability of the MB model. It clarifies the physical reasons for the large increase in T(c) for thick films, and it is shown that the experimental results are in good agreement with the predictions based on the monodomain model of Pertsev et al. [Phys. Rev. Lett. 80, 1988 (1998)].

Creating an Inclusive Society… How Close are We in Relation to Autism Spectrum Disorder? A General Population Survey

BackgroundChildren with autism spectrum disorder are increasingly educated in mainstream classrooms in the United Kingdom (Wilkinson & Twist, Autism and Educational Assessment: UK Policy and Practice. NFER, Slough, 2010), and some employers are now specifically seeking out staff on the autism spectrum. Does that mean that we are living in an inclusive society' [United Nations Department of Economic and Social Affairs (UNDESA), Creating an Inclusive Society: Practical Strategies to Promote Social Integration 2008], in the sense that inequalities are reduced and full economic, social and cultural participation is advanced for individuals with autism?

MethodsA general population survey was conducted to assess how close we, as a society, are to an inclusive society for individuals with autism in Northern Ireland. Public attitudes were examined to (i) visibility and social interaction, (ii) aetiology, needs and interventions, and (iii) rights and resources.

ResultsA stratified, representative sample of 1204 adults took part in the survey; of these, 989 were aware of autism and their attitudes and behavioural projections reflected a mix of acceptance and denunciation. The level of confusion with regard to interventions reflected the general uncertainty within UK policy regarding meeting the needs of individuals on the autism spectrum (International Journal of Disability, Development and Education 61, 134, 2014a).

ConclusionTherefore, it seems that inclusion is working to an extent, but more clarity is needed with regard to adequate education, intervention and support for individuals with autism.

Enrichment of low-abundance proteins from bovine and porcine serum samples for proteomic studies

One of the main applications of serum proteomics is the identification of new biomarkers for animal disease or animal production. However, potential obstacles to these studies are the poor performance of affinity serum depletion methods based on human antigens when using animal samples, and loss of minor serum components bound to albumin and other proteins. In the present study, we have analyzed the efficiency and reproducibility of the ProteoMiner® beads with bovine and porcine serum samples, and compared to a traditional immunoaffinity-based albumin and IgG depletion system specific for human samples. The ProteoMiner kit is based on the use of a combinatorial peptide binding library and intends to enrich low-abundance proteins.

Analogies to semantic and syntactic mental labour in the Feist decision

The Supreme Court of the United States in Feist v. Rural (Feist, 1991) specified that compilations or databases, and other works, must have a minimal degree of creativity to be copyrightable. The significance and global diffusion of the decision is only matched by the difficulties it has posed for interpretation. The judgment does not specify what is to be understood by creativity, although it does give a full account of the negative of creativity, as ‘so mechanical or routine as to require no creativity whatsoever’ (Feist, 1991, p.362). The negative of creativity as highly mechanical has particularly diffused globally.

A recent interpretation has correlated ‘so mechanical’ (Feist, 1991) with an automatic mechanical procedure or computational process, using a rigorous exegesis fully to correlate the two uses of mechanical. The negative of creativity is then understood as an automatic computation and as a highly routine process. Creativity is itself is conversely understood as non-computational activity, above a certain level of routinicity (Warner, 2013).

The distinction between the negative of creativity and creativity is strongly analogous to an independently developed distinction between forms of mental labour, between semantic and syntactic labour. Semantic labour is understood as human labour motivated by considerations of meaning and syntactic labour as concerned solely with patterns. Semantic labour is distinctively human while syntactic labour can be directly humanly conducted or delegated to machine, as an automatic computational process (Warner, 2005; 2010, pp.33-41).

The value of the analogy is to greatly increase the intersubjective scope of the distinction between semantic and syntactic mental labour. The global diffusion of the standard for extreme absence of copyrightability embodied in the judgment also indicates the possibility that the distinction fully captures the current transformation in the distribution of mental labour, where syntactic tasks which were previously humanly performed are now increasingly conducted by machine.

The paper has substantive and methodological relevance to the conference themes. Substantively, it is concerned with human creativity, with rationality as not reducible to computation, and has relevance to the language myth, through its indirect endorsement of a non-computable or not mechanical semantics. These themes are supported by the underlying idea of technology as a human construction. Methodologically, it is rooted in the humanities and conducts critical thinking through exegesis and empirically tested theoretical development

References

Feist. (1991). Feist Publications, Inc. v. Rural Tel. Service Co., Inc. 499 U.S. 340.

Warner, J. (2005). Labor in information systems. Annual Review of Information Science and Technology. 39, 2005, pp.551-573.

Warner, J. (2010). Human Information Retrieval (History and Foundations of Information Science Series). Cambridge, MA: MIT Press.

Warner, J. (2013). Creativity for Feist. Journal of the American Society for Information Science and Technology. 64, 6, 2013, pp.1173-1192.

Climate change response in Europe: What's the reality? Analysis of adaptation and mitigation plans from 200 urban areas in 11 countries

Urban areas are pivotal to global adaptation and mitigation efforts. But how do cities actually perform in terms of climate change response? This study sheds light on the state of urban climate change adaptation and mitigation planning across Europe. Europe is an excellent test case given its advanced environmental policies and high urbanization. We performed a detailed analysis of 200 large and medium-sized cities across 11 European countries and analysed the cities' climate change adaptation and mitigation plans. We investigate the regional distribution of plans, adaptation and mitigation foci and the extent to which planned greenhouse gas (GHG) reductions contribute to national and international climate objectives. To our knowledge, it is the first study of its kind as it does not rely on self-assessment (questionnaires or social surveys). Our results show that 35 % of European cities studied have no dedicated mitigation plan and 72 % have no adaptation plan. No city has an adaptation plan without a mitigation plan. One quarter of the cities have both an adaptation and a mitigation plan and set quantitative GHG reduction targets, but those vary extensively in scope and ambition. Furthermore, we show that if the planned actions within cities are nationally representative the 11 countries investigated would achieve a 37 % reduction in GHG emissions by 2050, translating into a 27 % reduction in GHG emissions for the EU as a whole. However, the actions would often be insufficient to reach national targets and fall short of the 80 % reduction in GHG emissions recommended to avoid global mean temperature rising by 2 °C above pre-industrial levels. © 2013 Springer Science+Business Media Dordrecht.

Resonantly Enhanced Multi-Photon Ionization Spectrum of the Neutral Green Fluorescent Protein Chromophore

The photophysics of the green fluorescent protein is governed by the electronic structure of the chromophore at the heart of its β-barrel protein structure. We present the first two-color, resonance-enhanced, multiphoton ionization spectrum of the isolated neutral chromophore in vacuo with supporting electronic structure calculations. We find the absorption maximum to be 3.65 ± 0.05 eV (340 ± 5 nm), which is blue-shifted by 0.5 eV (55 nm) from the absorption maximum of the protein in its neutral form. Our results show that interactions between the chromophore and the protein have a significant influence on the electronic structure of the neutral chromophore during photoabsorption and provide a benchmark for the rational design of novel chromophores as fluorescent markers or photomanipulators.