Understanding metabolic flux behaviour in whole-cell model output

Whole-cell modelling is a newly expanding field that has many applications in lab experiment design and predictive drug testing. Although whole-cell model output contains a wealth of information, it is complex and high dimensional and thus hard to interpret. Here, we present an analysis pipeline that combines machine learning, dimensionality reduction, and network analysis to interpret and visualise metabolic reaction fluxes from a set of single gene knockouts simulated in the Mycoplasma genitalium whole-cell model. We found that the reaction behaviours show trends that correlate with phenotypic classes of the simulation output, highlighting particular cellular subsystems that malfunction after gene knockouts. From a graphical representation of the metabolic network, we saw that there is a set of reactions that can be used as markers of a phenotypic class, showing their importance within the network. Our analysis pipeline can support the understanding of the complexity of in silico cells without detailed knowledge of the constituent parts, which can help to understand the effects of gene knockouts and, as whole-cell models become more widely built and used, aid genome design

Characterisation of penA and tetM resistance genes of Neisseria gonorrhoeae isolated in southern Africa - epidemiological monitoring and resistance development

Objective. To investigate penA and tetM resistance gene variation of Neisseria gonorrhoeae in order to define gene types for epidemiological monitoring and resistance development. Design. Isolates of N. gonorrhoeae which were susceptible and resistant to penicillin and/or tetracycline were selected. Strains comprised South African isolates (22 from Bloemfontein, 13 from Transvaal, 20 from the Cape) and 15 Botswana and 4 Namibia isolates. The penA genes (2 kb) of all strains and tetM genes (765 bp) of 11 high-level tetracycline-resistant strains were amplified and restricted with Hpall. Results and conclusions. Twelve different Hpall fingerprint patterns were obtained from the 74 isolates analysed for penicillin-binding protein (PBP) 2 gene (penA) alterations. Focusing on the transpeptidase domain, 25 isolates (3 whole gene patterns, minimal inhibitory concentrations (MICs) ~ 0,03 - 0,125 ug/ml) had restriction sites equivalent to those previously described for a susceptible strain. Of the remaining 9 PBP 2 'gene groups, 25 strains fell into a designated group E. Penicillin/ penicillin + clavulanic acid MICs determined on these group E isolates gave a range of 0,125 - 2,0 ug/ml, although MICs against 4 strains were ~ 0,03 ug/ml. MICs of penicillin/penicillin + c1avulanic acid for the 24 isolates that contained altered PBP 2 transpeptidase gene regions not designated group E were only ~ 0,03 - 0,125 ug/ml. The lack of a Hpall restriction site at nucleotide 1934 in the PBP 2 gene of group E strains was indicative of a small terminal region of N. cinerea DNA. This gene block, which was found in all the southern African areas studied, appears to predispose isolates to increased penicillin resistance. The 25,2 MDa conjugative plasmid carrying the tetM resistance determinant was readily demonstrated in 11 Botswana Namibia isolates exhibiting high-level resistance to tetracycline (MICs > 16 ug/ml). The tetM gene was shown to be of the American type

Statewide retrospective study of low acuity emergency presentations in New South Wales, Australia: who, what, where and why?

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Abstract Objective The present study aims to use a statewide population-based registry to assess the prevalence of low acuity emergency department (ED) presentations, describe the trend in presentation rates and to determine whether they were associated with various presentation characteristics such as the type of hospital as well as clinical and demographic variables. Design and setting This was a retrospective analysis of a population-based registry of ED presentations in New South Wales (NSW). Generalised estimating equations with log links were used to determine factors associated with low acuity presentations to account for repeat presentations and the possibility of clustering of outcomes. Participants Patients were included in this analysis if they presented to an ED between January 2010 and December 2014. The outcomes of interest were low acuity presentation, defined as those who self-presented (were not transported by ambulance), were assigned a triage category of 4 or 5 (semiurgent or non-urgent) and discharged back to usual residence from ED. Results There were 10.7 million ED presentations analysed. Of these, 45% were classified as a low acuity presentation. There was no discernible increase in the rate of low acuity presentations across NSW between 2010 and 2014. The strongest predictors of low acuity ED presentation were age <40 years of age (OR 1.77); injury or musculoskeletal administrative and non-urgent procedures (OR 2.96); ear, nose and throat, eye or oral (OR 5.53); skin or allergy-type presenting problems (OR 2.84). Conclusions Low acuity ED presentations comprise almost half of all ED presentations. Alternative emergency models of care may help meet the needs of these patients

Impact of The Daily Mile on children's physical and mental health, and educational attainment in primary schools: iMprOVE cohort study protocol

INTRODUCTION: School-based active mile initiatives such as The Daily Mile (TDM) are widely promoted to address shortfalls in meeting physical activity recommendations. The iMprOVE Study aims to examine the impact of TDM on children's physical and mental health and educational attainment throughout primary school. METHODS AND ANALYSIS: iMprOVE is a longitudinal quasi-experimental cohort study. We will send a survey to all state-funded primary schools in Greater London to identify participation in TDM. The survey responses will be used for non-random allocation to either the intervention group (Daily Mile schools) or to the control group (non-Daily Mile schools). We aim to recruit 3533 year 1 children (aged 5-6 years) from 77 primary schools and follow them up annually until the end of their primary school years. Data collection taking place at baseline (children in school year 1) and each primary school year thereafter includes device-based measures of moderate-to-vigorous physical activity (MVPA) and questionnaires to measure mental health (Strengths and Difficulties Questionnaire) and educational attainment (ratings from 'below expected' to 'above expected levels'). The primary outcome is the mean change in MVPA minutes from baseline to year 6 during the school day among the intervention group compared with controls. We will use multilevel linear regression models adjusting for sociodemographic data and participation in TDM. The study is powered to detect a 10% (5.5 min) difference between the intervention and control group which would be considered clinically significant. ETHICS AND DISSEMINATION: Ethics has been approved from Imperial College Research Ethics Committee, reference 20IC6127. Key findings will be disseminated to the public through research networks, social, print and media broadcasts, community engagement opportunities and schools. We will work with policy-makers for direct application and impact of our findings

Impact of The Daily Mile on children's physical and mental health, and educational attainment in primary schools: iMprOVE cohort study protocol.

Funder: Cancer Research UKFunder: British Heart FoundationIntroductionSchool-based active mile initiatives such as The Daily Mile (TDM) are widely promoted to address shortfalls in meeting physical activity recommendations. The iMprOVE Study aims to examine the impact of TDM on children's physical and mental health and educational attainment throughout primary school. METHODS AND ANALYSIS: iMprOVE is a longitudinal quasi-experimental cohort study. We will send a survey to all state-funded primary schools in Greater London to identify participation in TDM. The survey responses will be used for non-random allocation to either the intervention group (Daily Mile schools) or to the control group (non-Daily Mile schools). We aim to recruit 3533 year 1 children (aged 5-6 years) from 77 primary schools and follow them up annually until the end of their primary school years. Data collection taking place at baseline (children in school year 1) and each primary school year thereafter includes device-based measures of moderate-to-vigorous physical activity (MVPA) and questionnaires to measure mental health (Strengths and Difficulties Questionnaire) and educational attainment (ratings from 'below expected' to 'above expected levels'). The primary outcome is the mean change in MVPA minutes from baseline to year 6 during the school day among the intervention group compared with controls. We will use multilevel linear regression models adjusting for sociodemographic data and participation in TDM. The study is powered to detect a 10% (5.5 min) difference between the intervention and control group which would be considered clinically significant.Ethics and disseminationEthics has been approved from Imperial College Research Ethics Committee, reference 20IC6127. Key findings will be disseminated to the public through research networks, social, print and media broadcasts, community engagement opportunities and schools. We will work with policy-makers for direct application and impact of our findings

Impact of The Daily Mile on children's physical and mental health, and educational attainment in primary schools: iMprOVE cohort study protocol.

Funder: Cancer Research UKFunder: British Heart FoundationIntroductionSchool-based active mile initiatives such as The Daily Mile (TDM) are widely promoted to address shortfalls in meeting physical activity recommendations. The iMprOVE Study aims to examine the impact of TDM on children's physical and mental health and educational attainment throughout primary school. METHODS AND ANALYSIS: iMprOVE is a longitudinal quasi-experimental cohort study. We will send a survey to all state-funded primary schools in Greater London to identify participation in TDM. The survey responses will be used for non-random allocation to either the intervention group (Daily Mile schools) or to the control group (non-Daily Mile schools). We aim to recruit 3533 year 1 children (aged 5-6 years) from 77 primary schools and follow them up annually until the end of their primary school years. Data collection taking place at baseline (children in school year 1) and each primary school year thereafter includes device-based measures of moderate-to-vigorous physical activity (MVPA) and questionnaires to measure mental health (Strengths and Difficulties Questionnaire) and educational attainment (ratings from 'below expected' to 'above expected levels'). The primary outcome is the mean change in MVPA minutes from baseline to year 6 during the school day among the intervention group compared with controls. We will use multilevel linear regression models adjusting for sociodemographic data and participation in TDM. The study is powered to detect a 10% (5.5 min) difference between the intervention and control group which would be considered clinically significant.Ethics and disseminationEthics has been approved from Imperial College Research Ethics Committee, reference 20IC6127. Key findings will be disseminated to the public through research networks, social, print and media broadcasts, community engagement opportunities and schools. We will work with policy-makers for direct application and impact of our findings

Making the user more efficient: Design for sustainable behaviour

User behaviour is a significant determinant of a product’s environmental impact; while engineering advances permit increased efficiency of product operation, the user’s decisions and habits ultimately have a major effect on the energy or other resources used by the product. There is thus a need to change users’ behaviour. A range of design techniques developed in diverse contexts suggest opportunities for engineers, designers and other stakeholders working in the field of sustainable innovation to affect users’ behaviour at the point of interaction with the product or system, in effect ‘making the user more efficient’. Approaches to changing users’ behaviour from a number of fields are reviewed and discussed, including: strategic design of affordances and behaviour-shaping constraints to control or affect energyor other resource-using interactions; the use of different kinds of feedback and persuasive technology techniques to encourage or guide users to reduce their environmental impact; and context-based systems which use feedback to adjust their behaviour to run at optimum efficiency and reduce the opportunity for user-affected inefficiency. Example implementations in the sustainable engineering and ecodesign field are suggested and discussed

The Effect of Using an Inappropriate Protein Database for Proteomic Data Analysis

A recent study by Bromenshenk et al., published in PLoS One (2010), used proteomic analysis to identify peptides purportedly of Iridovirus and Nosema origin; however the validity of this finding is controversial. We show here through re-analysis of a subset of this data that many of the spectra identified by Bromenshenk et al. as deriving from Iridovirus and Nosema proteins are actually products from Apis mellifera honey bee proteins. We find no reliable evidence that proteins from Iridovirus and Nosema are present in the samples that were re-analyzed. This article is also intended as a learning exercise for illustrating some of the potential pitfalls of analysis of mass spectrometry proteomic data and to encourage authors to observe MS/MS data reporting guidelines that would facilitate recognition of analysis problems during the review process