Inferring the conservative causal core of gene regulatory networks

Background
Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically.

Results
In this paper, we introduce a novel gene regulatory network inference (GRNI) algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently.

Conclusions
For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

Value creation and value claiming in strategic outsourcing decisions: A resource contingency perspective

This study integrates the concepts of value creation and value claiming into a theoretical framework that emphasizes the dependence of resource value maximization on value-claiming motivations in outsourcing decisions. To test this theoretical framework, it develops refutable implications to explain the firm's outsourcing decision, and it uses data from 178 firms in the publishing and printing industry on outsourcing of application services. The results show that in outsourcing decisions, resource value and transaction costs are simultaneously considered and that outsourcing decisions are dependent on alignment between resource and transaction attributes. The findings support a resource contingency view that highlights value-claiming mechanisms as resource contingency in interorganizational strategic decisions.

Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy

Prior family and adoption studies have suggested a genetic relationship between schizophrenia and schizotypy. However, this has never been verified using linkage methods. We therefore attempted to test for a correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. The Irish study of high-density schizophrenia families comprises 270 families with at least two members with schizophrenia or poor-outcome schizoaffective disorder (n = 637). Non-psychotic relatives were assessed using the structured interview for schizotypy (n = 746). A 10-cM multipoint, non-parametric, autosomal genomewide scan of schizophrenia was performed in Merlin. A scan of a quantitative trait comprising ratings of DSM-III-R criteria for schizotypal personality disorder in non-psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD) scores were regressed onto schizophrenia LOD scores at all loci, with adjustment for spatial autocorrelation. To assess empirical significance, this was also carried out using 1000 null scans of schizotypy. The number of jointly linked loci in the real data was compared to distribution of jointly linked loci in the null scans. No markers were suggestively linked to schizotypy based on strict Lander Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above chance expectation genome wide (empirical P = 0.04). Two and four loci yielded nonparametric LOD (NPLs) > 1.0 and > 0.75, respectively, for both schizophrenia and schizotypy (genome-wide empirical P = 0.04 and 0.02, respectively). These results suggest that at least a subset of schizophrenia susceptibility genes also affects schizotypy in non-psychotic relatives. Power may therefore be increased in molecular genetic studies of schizophrenia if they incorporate measures of schizotypy in non-psychotic relatives.

A total Indifference to Our Dignity: Older People's Understanding of Elder Abuse

Findings show that the current definitions of elder abuse, which centre on the actions or inactions of a person or persons where there is an expectation of trust, ignore wider societal issues like the withdrawal of respect and recognition. This serves to place older people in vulnerable positions.
Standard typologies of abuse were recognised by participants, although sexual abuse was not commonly mentioned except when prompted. However, what also emerged was a new concept of ‘personhood abuse’. This refers to societal attitudes; how these affect a person’s confidence, autonomy and agency resulting in an inability to say no or to stand up for oneself against abusive
acts, words and pressures possibly from fear of negative repercussions such as withdrawal of contact and/or care. Many ways were identified to support older people and reduce the opportunity for abusive actions to occur. They centred on community-based and peer supports through ‘having someone to talk
to’ and being aware of their rights. Continued involvement in community based activity which keeps people active and participating in society, such as community transport and clubs, supported people’s access to amenities and opportunities for engagement and were identified as ways to
prevent abuse from happening. Enhanced status, resources and support therefore need to be given to these types of community activities to prevent abuse occurring in the first place. These types of supports can enable older people to share their concerns in an everyday setting and to gain informal support and confidence; seeking more formal interventions when necessary.

Nonrigid Structure-From-Motion From 2-D Images Using Markov Chain Monte Carlo

In this paper we present a new method for simultaneously determining three dimensional (3-D) shape and motion of a non-rigid object from uncalibrated two dimensional (2- D) images without assuming the distribution characteristics. A non-rigid motion can be treated as a combination of a rigid rotation and a non-rigid deformation. To seek accurate recovery of deformable structures, we estimate the probability distribution function of the corresponding features through random sampling, incorporating an established probabilistic model. The fitting between the observation and the projection of the estimated 3-D structure will be evaluated using a Markov chain Monte Carlo based expectation maximisation algorithm. Applications of the proposed method to both synthetic and real image sequences are demonstrated with promising results.

Regenerative Medicine and New Labour Life Science Policy: Rhetorics of Success, Narratives of Sustainability and Survival

Advances in stem cell science and tissue engineering are being turned into applications and products through a novel medical paradigm known as regenerative medicine. This paper begins by examining the vulnerabilities and risks encountered by the regenerative medicine industry during a pivotal moment in its scientific infancy: the 2000s. Under the auspices of New Labour, British medical scientists and life science innovation firms associated with regenerative medicine, received demonstrative rhetorical pledges of support, aligned with the publication of a number of government initiated reports presaged by Bioscience 2015: Improving National Health, Increasing National Wealth. The Department of Health and the Department of Trade and Industry (and its successors) held industry consultations to determine the best means by which innovative bioscience cultures might be promoted and sustained in Britain. Bioscience 2015 encapsulates the first chapter of this sustainability narrative. By 2009, the tone of this storyline had changed to one of survivability. In the second part of the paper, we explore the ministerial interpretation of the ‘bioscience discussion cycle’ that embodies this narrative of expectation, using a computer-aided content analysis programme. Our analysis notes that the ministerial interpretation of these reports has continued to place key emphasis upon the distinctive and exceptional characteristics of the life science industries, such as their ability to perpetuate innovations in regenerative medicine and the optimism this portends – even though many of the economic expectations associated with this industry have remained unfulfilled.

Does first aid have a place in the medical curriculum? A survey of medical students

Introduction: When a medical emergency occurs in the prehospital environment, there is an expectation from the general public for medical students to offer assistance with a similar level of competence as qualified doctors. However, the question is raised; do medical students have sufficient training in first aid skills to fulfil the role expected of them?

Prior to the publication of the latest version of Tomorrow’s Doctors by the UK General Medical Council, a student selected component (SSC) in first aid was delivered at the medical school in Queen’s University Belfast (QUB), Northern Ireland. The overwhelming popularity of this SSC prompted a desire to investigate and understand students’ experiences of first aid.

Aim: To identify first and second year medical students’ knowledge of, and attitudes towards, first aid and their expectations of the medical curriculum.

Methods: A questionnaire was delivered using TurningPoint Audience Response System® during the second semester of the 2008 - 2009 academic year to all first and second year medical students at QUB.

Results: Less than half of the students felt that they had a good level of first aid knowledge, a third would feel confident helping in an emergency and only 10% would be confident leading an emergency situation. The vast majority of students believed first aid is beneficial, that the general public expect medical students to have the knowledge to handle an emergency situation, and that a full first aid course should be included in the core medical curriculum at an early stage. They did not believe it should be a pre-requisite for medical school.

Conclusion: Only a small proportion believed their first aid knowledge adequate. An overwhelming proportion believed that first aid training is beneficial and that the public expect competency in managing emergencies. This study clearly demonstrates students’ need and desire for first aid training in the core medical curriculum at an early stage and to the highest training level possible.

The Diffusion of Risks in Public Private Partnership Contracts

Purpose The UK government argues that the benefits of public private partnership (PPP) in delivering public infrastructure stem from: transferring risks to the private sector within a structure in which financiers put their own capital at risk; and, the performance based payment mechanism, reinforced by the due diligence requirements imposed by the lenders financing the projects (HM Treasury, 2010). Prior studies of risk in PPPs have investigated ‘what’ risks are allocated and to ‘whom’, that is to the public or the private sector. The purpose of this study is to examine ‘how’ and ‘why’ PPP risks are diffused by their financiers. Design/methodology/approach This study focuses on the financial structure of PPPs and on their financiers. Empirical evidence comes from interviews conducted with equity and debt financiers. Findings The findings show that the financial structure of the deals generates risk aversion in both debt and equity financiers and that the need to attract affordable finance leads to risk diffusion through a network of companies using various means that include contractual mitigation through insurance, performance support guarantees, interest rate swaps and inflation hedges. Because of the complexity this process generates, both procurers and suppliers need expensive expert advice. The risk aversion and diffusion and the consequent need for advice add cost to the projects impacting on the government’s economic argument for risk transfer. Limitations and implications The empirical work covers the private finance initiative (PFI) type of PPP arrangements and therefore the risk diffusion mechanisms may not be generalisable to other forms of PPP, especially those that do not involve the use of high leverage or private finance. Moreover, the scope of this research is limited to exploring the diffusion of risk in the private sector. Further research is needed on how risk is diffused in other settings and on the value for money implication of risk diffusion in PPP contracts. Originality/value The expectation inherent in PPP is that the private sector will better manage those risks allocated to it and because private capital is at risk, financiers will perform due diligence with the ultimate outcome that only viable projects will proceed. This paper presents empirical evidence that raises questions about these expectations. Key words: public private partnership, risk management, diffusion, private finance initiative, financiers

Random Regret Minimization: Exploration of a New Choice Model for Environmental and Resource Economics

This paper introduces the discrete choice model-paradigm of Random Regret Minimization (RRM) to the field of environmental and resource economics. The RRM-approach has been very recently developed in the context of travel demand modelling and presents a tractable, regret-based alternative to the dominant choice-modelling paradigm based on Random Utility Maximization-theory (RUM-theory). We highlight how RRM-based models provide closed form, logit-type formulations for choice probabilities that allow for capturing semi-compensatory behaviour and choice set-composition effects while being equally parsimonious as their utilitarian counterparts. Using data from a Stated Choice-experiment aimed at identifying valuations of characteristics of nature parks, we compare RRM-based models and RUM-based models in terms of parameter estimates, goodness of fit, elasticities and consequential policy implications.

AVEC 2011–The First International Audio/Visual Emotion Challenge

The Audio/Visual Emotion Challenge and Workshop (AVEC 2011) is the first competition event aimed at comparison of multimedia processing and machine learning methods for automatic audio, visual and audiovisual emotion analysis, with all participants competing under strictly the same conditions. This paper first describes the challenge participation conditions. Next follows the data used – the SEMAINE corpus – and its partitioning into train, development, and test partitions for the challenge with labelling in four dimensions, namely activity, expectation, power, and valence. Further, audio and video baseline features are introduced as well as baseline results that use these features for the three sub-challenges of audio, video, and audiovisual emotion recognition.

Electron refluxing and K-shell line emission from Ti foils irradiated with sub-picosecond laser pulses at 527nm

We present data on emission of K-shell radiation from Ti foils irradiated with subpicosecond pulses of second harmonic radiation (527 nm) from the TARANIS laser system at intensities of up to 1018 Wcm-2. The data are used to demonstrate that a resonance absorption type mechanism is responsible for absorption of the laser light and to estimate fast electron temperatures of 30–60 keV that are in broad agreement with expectation from models of absorption for a steep density gradient. Data taken with resin-backed targets are used to demonstrate clear evidence of electron refluxing even at the modest fast electron temperatures inferred.

The role of regret minimisation in lifestyle choices affecting the risk of coronary heart disease

This paper introduces the discrete choice model-paradigm of Random Regret Minimisation (RRM) to the field of health economics. The RRM is a regret-based model that explores a driver of choice different from the traditional utility-based Random Utility Maximisation (RUM). The RRM approach is based on the idea that, when choosing, individuals aim to minimise their regret–regret being defined as what one experiences when a non-chosen alternative in a choice set performs better than a chosen one in relation to one or more attributes. Analysing data from a discrete choice experiment on diet, physical activity and risk of a fatal heart attack in the next ten years administered to a sample of the Northern Ireland population, we find that the combined use of RUM and RRM models offer additional information, providing useful behavioural insights for better informed policy appraisal.

The influence of evidence-based medicine training on decision-making in relation to over-the-counter medicines: a qualitative study

Objectives
To explore the role of evidence of effectiveness when making decisions about over-the-counter (OTC) medication and to ascertain whether evidence-based medicine training raised awareness in decision-making. Additionally, this work aimed to complement the findings of a previous study because all participants in this current study had received training in evidence-based medicine (unlike the previous participants).

Methods
Following ethical approval and an e-mailed invitation, face-to-face, semi-structured interviews were conducted with newly registered pharmacists (who had received training in evidence-based medicine as part of their MPharm degree) to discuss the role of evidence of effectiveness with OTC medicines. Interviews were recorded and transcribed verbatim. Following transcription, all data were entered into the NVivo software package (version 8). Data were coded and analysed using a constant comparison approach.

Key findings
Twenty-five pharmacists (7 males and 18 females; registered for less than 4 months) were recruited and all participated in the study. Their primary focus with OTC medicines was safety; sales of products (including those that lack evidence of effectiveness) were justified provided they did no harm. Meeting patient expectation was also an important consideration and often superseded evidence. Despite knowledge of the concept, and an awareness of ethical requirements, an evidence-based approach was not routinely implemented by these pharmacists. Pharmacists did not routinely utilize evidence-based resources when making decisions about OTC medicines and some felt uncomfortable discussing the evidence-base for OTC products with patients.

Conclusions
The evidence-based medicine training that these pharmacists received appeared to have limited influence on OTC decision-making. More work could be conducted to ensure that an evidence-based approach is routinely implemented in practice

Atomic harmonic generation in time-dependent R-matrix theory

We have developed the capability to determine accurate harmonic spectra for multielectron atoms within time-dependent R-matrix (TDRM) theory. Harmonic spectra can be calculated using the expectation value of the dipole length, velocity, or acceleration operator. We assess the calculation of the harmonic spectrum from He irradiated by 390-nm laser light with intensities up to 4 x 10(14) W cm(-2) using each form, including the influence of the multielectron basis used in the TDRM code. The spectra are consistent between the different forms, although the dipole acceleration calculation breaks down at lower harmonics. The results obtained from TDRM theory are compared with results from the HELIUM code, finding good quantitative agreement between the methods. We find that bases which include pseudostates give the best comparison with the HELIUM code, but models comprising only physical orbitals also produce accurate results.

Material Deprivation, Economic Stress, and Reference Groups in Europe: An Analysis of EU-SILC 2009

In this article, we take advantage of the recent availability of data from the special module on material deprivation in the 2009 European Union Statistics on Income and Living Conditions to develop a more comprehensive understanding of the relationship between material deprivation and economic stress, the mediating and moderating roles played by cross-national differences in levels of income and income inequality, and the implications for competing perspectives on the nature of reference groups in Europe. The article establishes the critical role of basic deprivation, relating to inability to enjoy customary standards of living, in influencing economic stress levels. National income levels and inequality had no direct influence on economic stress. However, the impact of basic deprivation was stronger in countries with higher levels of income, indicating the crucial role of national reference groups. An interaction between basic deprivation and income inequality was also observed. However, contrary to the expectation that experiencing basic deprivation in a national context of high income inequality is likely to be particularly stressful, the consequences of such deprivation were most negative in low inequality countries. Experiencing basic deprivation where high income levels and lower inequality would lead to the expectation that such deprivation is eminently avoidable exacerbates its impact. © The Author 2013.