Oesophageal cancer: an overview of a deadly disease

Oesophageal cancer (OC) is one of the deadliest cancers in the world. Although it affects many people throughout East Africa, relatively little work has been done to fully understand this disease. This review addresses recent changes in the understanding of OC from a global perspective, with special attention given to OC in Kenya

Rapid, Heuristic Discovery and Design of Promoter Collections in Non-Model Microbes for Industrial Applications

This is the author accepted manusript. The final version is available from American Chemical Society via the DOI in this recordAccession Codes: The sequence data for the four Geobacillus spp. used in this study have been submitted to the NCBI Sequence Read Archive and are available under the accession number PRJNA521450.Well-characterized promoter collections for synthetic biology applications are not always available in industrially relevant hosts. We developed a broadly applicable method for promoter identification in atypical microbial hosts that requires no a priori understanding of cis-regulatory element structure. This novel approach combines bioinformatic filtering with rapid empirical characterization to expand the promoter toolkit and uses machine learning to improve the understanding of the relationship between DNA sequence and function. Here, we apply the method in Geobacillus thermoglucosidasius, a thermophilic organism with high potential as a synthetic biology chassis for industrial applications. Bioinformatic screening of G. kaustophilus, G. stearothermophilus, G. thermodenitrificans, and G. thermoglucosidasius resulted in the identification of 636 100 bp putative promoters, encompassing the genome-wide design space and lacking known transcription factor binding sites. Eighty of these sequences were characterized in vivo, and activities covered a 2-log range of predictable expression levels. Seven sequences were shown to function consistently regardless of the downstream coding sequence. Partition modeling identified sequence positions upstream of the canonical -35 and -10 consensus motifs that were predicted to strongly influence regulatory activity in Geobacillus, and artificial neural network and partial least squares regression models were derived to assess if there were a simple, forward, quantitative method for in silico prediction of promoter function. However, the models were insufficiently general to predict pre hoc promoter activity in vivo, most probably as a result of the relatively small size of the training data set compared to the size of the modeled design space

A Hybrid Sequencing Approach Completes the Genome Sequence of Thermoanaerobacter ethanolicus JW 200

This is the final version. Available on open access from American Society for Microbiology via the DOI in this recordData availability.The complete genome sequence of T. ethanolicus JW 200 is deposited in GenBank under the accession number CP033580. Illumina and Oxford Nanopore DNA sequence reads have been deposited in the NCBI Sequence Read Archive (accession numbers SRR8113455 and SRR8113456).Thermoanaerobacter ethanolicus JW 200 has been identified as a potential sustainable biofuel producer due to its ability to readily ferment carbohydrates to ethanol. A hybrid sequencing approach, combining Oxford Nanopore and Illumina DNA sequence reads, was applied to produce a single contiguous genome sequence of 2,911,280 bp.Shell Research Ltd

Using gamma+jets Production to Calibrate the Standard Model Z(nunu)+jets Background to New Physics Processes at the LHC

The irreducible background from Z(nunu)+jets, to beyond the Standard Model searches at the LHC, can be calibrated using gamma+jets data. The method utilises the fact that at high vector boson pT, the event kinematics are the same for the two processes and the cross sections differ mainly due to the boson-quark couplings. The method relies on a precise prediction from theory of the Z/gamma cross section ratio at high pT, which should be insensitive to effects from full event simulation. We study the Z/gamma ratio for final states involving 1, 2 and 3 hadronic jets, using both the leading-order parton shower Monte Carlo program Pythia8 and a leading-order matrix element program Gambos. This enables us both to understand the underlying parton dynamics in both processes, and to quantify the theoretical systematic uncertainties in the ratio predictions. Using a typical set of experimental cuts, we estimate the net theoretical uncertainty in the ratio to be of order 7%, when obtained from a Monte Carlo program using multiparton matrix-elements for the hard process. Uncertainties associated with full event simulation are found to be small. The results indicate that an overall accuracy of the method, excluding statistical errors, of order 10% should be possible.Comment: 22 pages, 14 figures; Accepted for publication by JHE

Effects of the physiological parameters on the signal-to-noise ratio of single myoelectric channel

<p>Abstract</p> <p>Background</p> <p>An important measure of the performance of a myoelectric (ME) control system for powered artificial limbs is the signal-to-noise ratio (SNR) at the output of ME channel. However, few studies illustrated the neuron-muscular interactive effects on the SNR at ME control channel output. In order to obtain a comprehensive understanding on the relationship between the physiology of individual motor unit and the ME control performance, this study investigates the effects of physiological factors on the SNR of single ME channel by an analytical and simulation approach, where the SNR is defined as the ratio of the mean squared value estimation at the channel output and the variance of the estimation.</p> <p>Methods</p> <p>Mathematical models are formulated based on three fundamental elements: a motoneuron firing mechanism, motor unit action potential (MUAP) module, and signal processor. Myoelectric signals of a motor unit are synthesized with different physiological parameters, and the corresponding SNR of single ME channel is numerically calculated. Effects of physiological multi factors on the SNR are investigated, including properties of the motoneuron, MUAP waveform, recruitment order, and firing pattern, etc.</p> <p>Results</p> <p>The results of the mathematical model, supported by simulation, indicate that the SNR of a single ME channel is associated with the voluntary contraction level. We showed that a model-based approach can provide insight into the key factors and bioprocess in ME control. The results of this modelling work can be potentially used in the improvement of ME control performance and for the training of amputees with powered prostheses.</p> <p>Conclusion</p> <p>The SNR of single ME channel is a force, neuronal and muscular property dependent parameter. The theoretical model provides possible guidance to enhance the SNR of ME channel by controlling physiological variables or conscious contraction level.</p

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

Unraveling the mysteries of dog evolution

The increased battery of molecular markers, derived from comparative genomics, is aiding our understanding of the genetics of domestication. The recent BMC Biology article pertaining to the evolution of small size in dogs is an example of how such methods can be used to study the origin and diversification of the domestic dog. We are still challenged, however, to appreciate the genetic mechanisms responsible for the phenotypic diversity seen in 'our best friend'

Palaeogenomics of the Hydrocarbon Producing Microalga Botryococcus braunii

This is the final version. Available from the publisher via the DOI in this record.Botryococcus braunii is a colonial microalga that appears early in the fossil record and is a sensitive proxy of environmental and hydroclimatic conditions. Palaeozoic Botryococcus fossils which contribute up to 90% of oil shales and approximately 1% of crude oil, co-localise with diagnostic geolipids from the degradation of source-signature hydrocarbons. However more recent Holocene sediments demonstrate no such association. Consequently, Botryococcus are identifed in younger sediments by morphology alone, where potential misclassifcations could lead to inaccurate paleoenvironmental reconstructions. Here we show that a combination of fow cytometry and ancient DNA (aDNA) sequencing can unambiguously identify Botryococcus microfossils in Holocene sediments with hitherto unparalleled accuracy and rapidity. The application of aDNA sequencing to microfossils ofers a far-reaching opportunity for understanding environmental change in the recent geological record. When allied with other high-resolution palaeoenvironmental information such as aDNA sequencing of humans and megafauna, aDNA from microfossils may allow a deeper and more precise understanding of past environments, ecologies and migrations.Medical Research Council (MRC)Wellcome TrustBiotechnology and Biological Science Research Council (BBSRC

Palaeogenomics of the Hydrocarbon Producing Microalga Botryococcus braunii.

Botryococcus braunii is a colonial microalga that appears early in the fossil record and is a sensitive proxy of environmental and hydroclimatic conditions. Palaeozoic Botryococcus fossils which contribute up to 90% of oil shales and approximately 1% of crude oil, co-localise with diagnostic geolipids from the degradation of source-signature hydrocarbons. However more recent Holocene sediments demonstrate no such association. Consequently, Botryococcus are identified in younger sediments by morphology alone, where potential misclassifications could lead to inaccurate paleoenvironmental reconstructions. Here we show that a combination of flow cytometry and ancient DNA (aDNA) sequencing can unambiguously identify Botryococcus microfossils in Holocene sediments with hitherto unparalleled accuracy and rapidity. The application of aDNA sequencing to microfossils offers a far-reaching opportunity for understanding environmental change in the recent geological record. When allied with other high-resolution palaeoenvironmental information such as aDNA sequencing of humans and megafauna, aDNA from microfossils may allow a deeper and more precise understanding of past environments, ecologies and migrations