Ab initio prediction of Boron compounds arising from Borozene: Structural and electronic properties

Structure and electronic properties of two unusual boron clusters obtained by fusion of borozene rings has been studied by means of first principles calculations, based on the generalized-gradient approximation of the density functional theory, and the semiempirical tight-binding method was used for the transport calculations. The role of disorder has also been considered with single vacancies and substitutional atoms. Results show that the pure boron clusters are topologically planar and characterized by (3c-2e) bonds, which can explain, together with the aromaticity (estimated by means of NICS), the remarkable cohesive energy values obtained. Such feature makes these systems competitive with the most stable boron clusters to date. On the contrary, the introduction of impurities compromises stability and planarity in both cases. The energy gap values indicate that these clusters possess a semiconducting character, while when the larger system is considered, zero-values of the density of states are found exclusively within the HOMO-LUMO gap. Electron transport calculations within the Landauer formalism confirm these indications, showing semiconductor-like low bias differential conductance for these stuctures. Differences and similarities with Carbon clusters are highlighted in the discussion.Comment: 10 pages, 2 tables, 5 figure

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Wood Dust in Joineries and Furniture Manufacturing: An Exposure Determinant and Intervention Study.

: To assess wood dust exposures and determinants in joineries and furniture manufacturing and to evaluate the efficacy of specific interventions on dust emissions under laboratory conditions. Also, in a subsequent follow-up study in a small sample of joinery workshops, we aimed to develop, implement, and evaluate a cost-effective and practicable intervention to reduce dust exposures. : Personal inhalable dust (n = 201) was measured in 99 workers from 10 joineries and 3 furniture-making factories. To assess exposure determinants, full-shift video exposure monitoring (VEM) was conducted in 19 workers and task-based VEM in 32 workers (in 7 joineries and 3 furniture factories). We assessed the efficacy of vacuum extraction on hand tools and the use of vacuum cleaners instead of sweeping and dry wiping under laboratory conditions. These measures were subsequently implemented in three joinery workshops with 'high' (&gt;4 mg m-3) and one with 'low' (&lt;2 mg m-3) baseline exposures. We also included two control workshops (one 'low' and one 'high' exposure workshop) in which no interventions were implemented. Exposures were measured 4 months prior and 4 months following the intervention. : Average (geometric means) exposures in joinery and furniture making were 2.5 mg m-3 [geometric standard deviations (GSD) 2.5] and 0.6 mg m-3 (GSD 2.3), respectively. In joinery workers cleaning was associated with a 3.0-fold higher (P &lt; 0.001) dust concentration compared to low exposure tasks (e.g. gluing), while the use of hand tools showed 3.0- to 11.0-fold higher (P &lt; 0.001) exposures. In furniture makers, we found a 5.4-fold higher exposure (P &lt; 0.001) with using a table/circular saw. Laboratory efficiency experiments showed a 10-fold decrease in exposure (P &lt; 0.001) when using a vacuum cleaner. Vacuum extraction on hand tools combined with a downdraft table reduced exposures by 42.5% for routing (P &lt; 0.1) and 85.5% for orbital sanding (P &lt; 0.001). Following intervention measures in joineries, a borderline statistically significant (P &lt; 0.10) reduction in exposure of 30% was found in workshops with 'high' baseline exposures, but no reduction was shown in the workshop with 'low' baseline exposures. : Wood dust exposure is high in joinery workers and (to a lesser extent) furniture makers with frequent use of hand tools and cleaning being key drivers of exposure. Vacuum extraction on hand tools and alternative cleaning methods reduced workplace exposures substantially, but may be insufficient to achieve compliance with current occupational exposure limits.<br/

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Prevalence of ocular and oculodermal melanocytosis in Spanish population with uveal melanoma

Producción CientíficaThe aim of this study was to determine the prevalence of ocular and oculodermal melanocytosis (ODM) among patients with uveal melanoma (UM) in a Spanish population. METHODS: Retrospective review of the medical records of patients with ODM among patients with UM. RESULTS: Ten (11 eyes) of 400 patients (2.7%) with UM associated had ODM. The mean age at diagnosis of UM among patients with ODM was 62 years. One patient had bilateral tumours. UM was diagnosed during a routine-examination in two cases. All tumours were medium (7/11) or large (4/11) in size, with a mean maximum base of 13 mm and height of 7 mm. No patient had extraocular extension or metastatic disease at diagnosis. Enucleation was done in five cases and I-125-brachytherapy in six. The mean follow-up was 43 months. One patient died because of metastasis 2 years after enucleation; one patient is currently on treatment of systemic metastasis 11 years after. CONCLUSIONS: ODM is more frequent in spanish population with UM than in American population. Despite the risk of UM in ODM, it is often diagnosed late when a conservative treatment is not indicated

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Unique reporter-based sensor platforms to monitor signalling in cells

Introduction: In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level. &lt;p/&gt;Methods: Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis. &lt;p/&gt;Findings: We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation. &lt;p/&gt;Conclusions: We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters