The evaluation of training oral and maxillofacial trainees in head and neck cancer doctor-patient communication using the Patient Concerns Inventory.

AbstractHead and neck cancer has a significant impact on a patient’s health related quality of life (HRQOL). The head and neck specific Patient Concerns Inventory (PCI-HN) has been utilised to enhance doctor-patient dialogue in routine consultations. To date there has been no formal training for oral and maxillofacial surgery (OMFS) surgical trainees in the use of the PCI-HN in consultations. The aim of the study was to evaluate training for OMFS surgical trainees in the use of the PCI-HN, using simulated follow-up HNC consultations, in order to improve doctor-patient communication skills.Material and methodsTen oral and maxillofacial surgical trainees completed actor simulated HNC consultations before and after training. A study-specific mark scheme was developed based on the ComOn-Coaching rating scales and used to score the doctor-patient interaction. A group debrief afterwards explored the trainee’s experiences of the training and consultations. ResultsAll trainees showed an improvement in doctor-patient communication scores following their training. Overall, the six participants who were Specialty registrars, year 3 (ST3) or above, scored higher, than the four Specialty registrars, year 1-2 (ST1-2). The scores were higher if fewer PCI-HN items were discussed (3-4). The most frequently avoided PCI-HN items were intimacy and relationships. The trainees considered that their training was useful for organising their consultations and for providing holistic care. ConclusionAlthough training improved surgeon-patient communication, further evaluation is required with a larger number of trainees and actual consultations in clinic.<br/

An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics

Electron backscatter diffraction analysis unveils foraminiferal calcite microstructure and processes of diagenetic alteration

Electron backscatter diffraction (EBSD) analysis enables a unique perspective of the internal microstructure of foraminiferal calcite. Specifically, EBSD provides crystallographic data from within the test, highlighting the highly organised “mesocrystal” structure of crystallographically aligned domains throughout the test, formed by sequential deposits of microgranular calcite. We compared EBSD maps across the test walls of both poorly preserved and well-preserved specimens of the planktonic foraminifera species Globigerinoides ruber and Morozovella crater. The EBSD maps, paired with information about intra-test distributions of Mg/Ca ratios, allowed us to examine the effects of different diagenetic processes on the foraminifera test. In poorly preserved specimens EBSD data show extensive reorganisation of the biogenic crystal microstructure, indicating differing phases of dissolution, re-precipitation and overgrowth. The specimens with the greatest degree of microstructural reorganisation also show an absence of higher concentration magnesium bands, which are typical features of well-preserved specimens. These findings provide important insights into the extent of post-depositional changes, in both microstructure and geochemical signals that must be considered when utilising foraminifera to generate proxy archive data

A DNA-barcode biodiversity standard analysis method (DNA-BSAM) reveals a large variance in the effect of a range of biological, chemical and physical soil management interventions at different sites, but location is one of the most important aspects determining the nature of agricultural soil microbiology

There are significant knowledge gaps in our understanding of how to sustainably manage agricultural soils to preserve soil biodiversity. Here we evaluate and quantify the effects of agricultural management and location on soil microbiology using nine field trials that have consistently applied different soil management practices in the United Kingdom using DNA barcode sequence data. We tested the basic hypothesis that various agricultural management interventions have a significant and greater effect on soil bacterial and fungal diversity than geographic location. The analyses of soil microbial DNA sequence data to date has lacked standardisation which prevents meaningful comparisons across sites and studies. Therefore, to analyse these data and crucially compare and quantify the size of any effects on soil bacterial and fungal biodiversity between sites, we developed and employed a post-sequencing DNA-barcode biodiversity standard analysis method (DNA-BSAM). The DNA-BSAM comprises a series of standardised bioinformatic steps for processing sequences but more importantly defines a standardised set of ecological indices and statistical tests. Use of the DNA-BSAM reveals the hypothesis was not strongly supported, and this was primarily because: 1) there was a large variance in the effects of various management interventions at different sites, and 2) that location had an equivalent or greater effect size than most management interventions for most metrics. Some dispersed sites imposed the same organic amendments interventions but showed different responses, and this combined with observations of strong differences in soil microbiomes by location tentatively suggests that any effect of management may be contingent on location. This means it could be unreliable to extrapolate the findings of individual trials to others. The widespread use of a standard approach will allow meaningful cross-comparisons between soil microbiome studies and thus a substantial evidence-base of the effects of land-use on soil microbiology to accumulate and inform soil management decisions.Agriculture and Horticulture Development Board (AHDB); British Beet Research Organisation (BBRO

Electron backscatter diffraction analysis unveils foraminiferal calcite microstructure and processes of diagenetic alteration

Electron backscatter diffraction (EBSD) analysis enables a unique perspective of the internal microstructure of foraminiferal calcite. Specifically, EBSD provides crystallographic data from within the test, highlighting the highly organised “mesocrystal” structure of crystallographically aligned domains throughout the test, formed by sequential deposits of microgranular calcite. We compared EBSD maps across the test walls of both poorly preserved and well-preserved specimens of the planktonic foraminifera species Globigerinoides ruber and Morozovella crater. The EBSD maps, paired with information about intra-test distributions of ratios, allowed us to examine the effects of different diagenetic processes on the foraminifera test. In poorly preserved specimens EBSD data show extensive reorganisation of the biogenic crystal microstructure, indicating differing phases of dissolution, re-precipitation and overgrowth. The specimens with the greatest degree of microstructural reorganisation also show an absence of higher concentration magnesium bands, which are typical features of well-preserved specimens. These findings provide important insights into the extent of post-depositional changes, in both microstructure and geochemical signals that must be considered when utilising foraminifera to generate proxy archive data

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

Ruminococcus gnavus is a human gut symbiont which ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid binding carbohydrate binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis, and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 b-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut

DNA Methylation Biomarkers Offer Improved Diagnostic Efficiency in Lung Cancer

The exceptional high mortality of lung cancer can be instigated to a high degree by late diagnosis. Despite the plethora of studies on potential molecular biomarkers for lung cancer diagnosis, very few have reached clinical implementation. In this study we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency in bronchial washings from a large retrospective cohort. Candidate targets from previous high-throughput approaches were examined by Pyrosequencing in an independent set of 48 lung tumor/normal paired. Ten promoters were selected and quantitative methylation-specific PCR (qMSP) assays were developed and used to screen 655 bronchial washings (BWs) from the Liverpool Lung Project (LLP) subjects divided into training (194 cases and 214 Controls) and validation (139 cases and 109 controls) sets. Three statistical models were employed to select the optimal panel of markers and evaluate the performance of the discriminatory algorithms. The final logit regression model incorporated hypermethylation at p16, TERT, WT1 and RASSF1.The performance of this 4-gene methylation signature in the validation set demonstrated 82% sensitivity and 91% specificity. In comparison, cytology alone in this set provided 43% sensitivity at 100% specificity. The diagnostic efficiency of the panel did not show any biases with age, gender, smoking and the presence of a non-lung neoplasm. However, sensitivity was predictably higher in central (squamous and small cell) than peripheral (adenocarcinomas) tumors, as well as in stage 2 or greater tumors.These findings clearly demonstrate the impact of DNA methylation-based assays in the diagnosis of cytologically occult lung neoplasms. A prospective trial is currently imminent in the LLP study to provide data on the enhancement of diagnostic accuracy in a clinical setting, including by additional markers

Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of > 90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal alpha 2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.Peer reviewe