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.

A national clinical scenario-based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients

Background: It is known that 20-30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non-bleeding coagulopathic critically ill patients.

Factors influencing patients with stage 5 chronic kidney disease to opt for conservative management: a practitioner research study

Aims and objectives. This study explored decision-making experiences of patients with stage 5 chronic kidney disease when opting for conservative management of their renal failure.

Background. Dialysis is an invasive treatment, and for some older patients, there is an associated treatment burden of dialysis-related symptoms. An alternative choice is conservative management, but little is known about those who make this decision and how they are supported through the process.

Design. Qualitative practitioner research study.

Method. Data were generated from nine patients' naturally occurring clinic consultations with a renal clinical nurse specialist between May 2010 - July 2010. Interviews were transcribed verbatim and findings fed back at three multi-disciplinary meetings to check for relevance and resonance. Common themes were identified and codes applied.

Results. Patients reported age and having to travel three times a week to hospital for dialysis as reasons not to opt for treatment. Others felt well without dialysis not wanting to upset the 'status quo' or to burden loved ones. Most felt equipped to make the decision following explanation and discussion with the clinical nurse specialist in the renal clinic.

Conclusions. Patients opting for conservative management give numerous reasons for this including old age, travel limitations, feeling well without dialysis and not wanting to be a burden, but appear content with their decision. One-to-one discussions with the clinical nurse specialist appear helpful during the decision-making process presenting an opportunity for advancing nursing roles in the chronic kidney disease service.

Relevance to clinical practice. Understanding patients' reasons for refusing dialysis assists in supporting until death. There is an opportunity for developing nursing practice to meet the multi-faceted needs of this group.

Comment on 'Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location'

A recent paper by Lechtman et al (2011 Phys. Med. Biol. 56 4631-47) presented Monte Carlo modelling of gold nanoparticle dose modification. In it, they predict that the introduction of gold nanoparticles has the strongest effect with x-rays at kilovoltage energies, and that negligible increases in dose are expected at megavoltage energies. While these results are in agreement with others in the literature (including those produced by our group), the conclusion that '(goldnanoparticle) radiosensitization using a 6 MV photon source is not clinically feasible' appears to conflict with recently published experimental studies which have shown radiosensitization using 6 MV x-ray sources with relatively low gold concentrations. The increasing disparity between theoretical predictions of dose enhancement and experimental results in the field of gold nanoparticle radiosensitization suggests that, while the ability of gold nanoparticles to modify dose within a tumour volume is well understood, the resulting radiosensitization is not simply correlated with this measure. This highlights the need to validate theoretical predictions of this kind against experimental measurements, to ensure that the scenarios and values being modelled are meaningful within a therapeutic context.

The Collapse Behaviour of Cold-formed Steel Portal Frames at Elevated Temperatures

This paper describes the results of non-linear elasto-plastic implicit dynamic finite element analyses that are used to predict the collapse behaviour of cold-formed steel portal frames at elevated temperatures. The collapse behaviour of a simple rigid-jointed beam idealisation and a more accurate semi-rigid jointed shell element idealisation are compared for two different fire scenarios. For the case of the shell element idealisation, the semi-rigidity of the cold-formed steel joints is explicitly taken into account through modelling of the bolt-hole elongation stiffness. In addition, the shell element idealisation is able to capture buckling of the cold-formed steel sections in the vicinity of the joints. The shell element idealisation is validated at ambient temperature against the results of full-scale tests reported in the literature. The behaviour at elevated temperatures is then considered for both the semi-rigid jointed shell and rigid-jointed beam idealisations. The inclusion of accurate joint rigidity and geometric non-linearity (second order analysis) are shown to affect the collapse behaviour at elevated temperatures. For each fire scenario considered, the importance of base fixity in preventing an undesirable outwards collapse mechanism is demonstrated. The results demonstrate that joint rigidity and varying fire scenarios should be considered in order to allow for conservative design.

The British conservative party and Europe:The choosing of John Major

This article provides an empirical analysis of voting behaviour in the second ballot of the 1990 Conservative leadership contest that resulted in John Major becoming party leader and prime minister. Seven hypotheses of voting behaviour are generated from the extant literature relating voting to socio-economic variables (occupational and educational background), political variables (parliamentary experience, career status, age and electoral marginality) and ideological variables (drawn from survey data on MPs' positions on economic, European and moral issues). These hypotheses are tested using data on voting intentions gathered from published lists of MPs' declarations, interviews with each of the leadership campaign teams, and correspondence with MPs. Bivariate relationships are presented, followed by logistic regression analysis to isolate the unique impact that each variable had on voting. This shows that educational background, parliamentary experience and (especially) attitudes to Europe were the key factors determining voting. The importance of Europe in the contest is particularly instructive: the severe problems for Major's leadership which were caused by the issue can be attributed to, and understood in the context of, the 1990 contest in which he became leader.