The integrated DL_POLY/DL_FIELD/DL_ANALYSER software platform for molecular dynamics simulations for exploration of the synthonic interactions in saturated benzoic acid/hexane solutions

Three separately developed software Molecular Dynamics packages at Daresbury Laboratory, namely DL_FIELD (DL_F), DL_POLY and DL_ANALYSER, have been integrated to form an efficient computational infrastructure to investigate the detailed solution chemistry of saturated benzoic acid in hexane solutions. These software capabilities are demonstrated, in combination with the Synthonic Engineering tools and density functional theory (DFT) calculations, to assess the extent that the solute-solute intermolecular synthonic interactions in solution mirrors the synthons in the crystal structure. The results show that the majority of the COOH groups are forming OH … O H-bonds, which are a combination of classic OH … O homo-dimers and three membered H-bonding clusters. The formation of pi-pi stacking interactions is observed, but in far fewer numbers than observed for the OH … O interactions. The DFT simulations of the IR spectra of the multiple benzoic acid aggregates extracted from the MD trajectories provides further in-depth analysis of previously published IR data, by matching simulated peaks to the experimental peaks, hence identifying the exact bonding modes that are responsible for such peaks. This study demonstrates the value of a multi-scale and multi-technique approach to exploring the molecular transition pathway from solution to crystal structure

Accuracy of Intravenous and Enteral Preparations Involving Small Volumes for Paediatric Use: A Review

Background: Children often need to be administered very small volumes of medicines that are authorised for use in adults. Neonatal drug delivery is particularly challenging and doses are often immeasurable with the equipment currently available. Aim: To summarise research to date on the accuracy of intravenous and enteral medicine preparation requiring small volumes (<0.1mL), with a focus on paediatric use and to identify areas for further work. Method: Twenty-three publications were identified for the narrative review via: Web of Science (1950-2016), Cumulative Index to Nursing and Allied Health Literature (1976-2016), Excerpta Medica Database (1974-2016) and International Pharmaceutical Abstracts (1970-2016) searches. Nine additional papers were identified through backward citation tracking and a further 17 were included from the personal knowledge of the review team. Results: Measurement of volumes (<0.1mL), for enteral and intravenous dosing, account for 25% of medicine manipulations within paediatric hospitals. Inaccuracies are described throughout the literature with dose administration errors attributed to technique, calculation, dilution and problems associated with equipment. Whilst standardised concentrations for intravenous infusion and drug concentrations which avoid measurement of small volumes would ameliorate problems, further work is needed to establish accurate methods for handling small volumes during the administration of medicines to children and risk minimisation strategies to support staff involved are also necessary. Conclusion: This review has revealed a paucity of information on the clinical outcomes from problems in measuring small volumes for children and highlighted the need for further work to eliminate this source of inaccurate dosing and potential for medication error

A preliminary audit of medical and aid provision in English Rugby union clubs:compliance with Regulation 9

BackgroundGoverning bodies are largely responsible for the monitoring and management of risks associated with a safe playing environment, yet adherence to regulations is currently unknown. The aim of this study was to investigate and evaluate the current status of medical personnel, facilities, and equipment in Rugby Union clubs at regional level in England.MethodsA nationwide cross-sectional survey of 242 registered clubs was undertaken, where clubs were surveyed online on their current medical personnel, facilities, and equipment provision, according to regulation 9 of the Rugby Football Union (RFU).ResultsOverall, 91 (45. 04%) surveys were returned from the successfully contacted recipients. Of the completed responses, only 23.61% (n = 17) were found to be compliant with regulations. Furthermore, 30.56% (n = 22) of clubs were unsure if their medical personnel had required qualifications; thus, compliance could not be determined. There was a significant correlation (p = −0.029, r = 0.295) between club level and numbers of practitioners. There was no significant correlation indicated between the number of practitioners/number of teams and number of practitioners/number of players. There were significant correlations found between club level and equipment score (p = 0.003, r = −0.410), club level and automated external defibrillator (AED) access (p = 0.002, r = −0.352) and practitioner level and AED access (p = 0.0001, r = 0.404). Follow-up, thematic analysis highlighted widespread club concern around funding/cost, awareness, availability of practitioners and AED training.ConclusionThe proportion of clubs not adhering overall compliance with Regulation 9 of the RFU is concerning for player welfare, and an overhaul, nationally, is required

Knowledge, attitude and practices of pediatricians regarding the prevention of oral diseases in Italy

BACKGROUND: Pediatricians are in an ideal position to advise families about the prevention and management of oral diseases in children. The objective of the study was to determine knowledge, attitude, and practices regarding the prevention of oral diseases among pediatricians in Italy. METHODS: A systematic random sample of 1000 pediatricians received a questionnaire on socio-demographic and practice characteristics; knowledge on risk factors; attitude and practices towards the prevention of oral diseases. RESULTS: A total of 507 pediatricians participated. More than half knew the main risk factors for oral diseases and this knowledge was higher in primary care pediatricians (p = 0.007), in those with a higher number of hours worked per week (p = 0.012), and who believed that oral diseases may be prevented (p = 0.017). Pediatricians with higher knowledge about the main risk factors (p = 0.006) believe that they have an important role in preventing oral diseases and that they can perform an oral examination. Almost all (89%) prescribed fluoride supplements and those younger (p = 0.016), with a higher number of patients seen in workday (p = 0.001), with longer practice activity (p = 0.004), those who believe that fluoride is effective in preventing caries (p < 0.0001), and who learned about prevention from scientific sources (p = 0.002) were more likely to prescribe fluoride. One-fourth and 40.6% provides and recommends a dental visit once a year and primary care pediatricians (p = 0.014) and those who believed that routine visit is important in preventing oral diseases (p < 0.0001) were more likely to recommend a dental visit once a year. CONCLUSION: The results showed a lack of knowledge among pediatricians although almost all believed that they had an important responsibility in preventing oral diseases and provided an oral examination

The impact of a single round of community mass treatment with azithromycin on disease severity and ocular Chlamydia trachomatis load in treatment-naïve trachoma-endemic island communities in West Africa.

BACKGROUND: Trachoma, a neglected tropical disease, is caused by ocular infection with Chlamydia trachomatis (Ct). The World Health Organization (WHO) recommends three annual rounds of community mass drug treatment with azithromycin (MDA) if the prevalence of follicular trachoma in 1-9 year olds (TF1-9) exceeds 10% at district level to achieve an elimination target of district-level TF1-9 below 5% after. To evaluate this strategy in treatment-naïve trachoma-endemic island communities in Guinea Bissau, we conducted a cross-sectional population-based trachoma survey on four islands. The upper tarsal conjunctivae of each participant were clinically assessed for trachoma and conjunctival swabs were obtained (n = 1507). We used a droplet digital PCR assay to detect Ct infection and estimate bacterial load. We visited the same households during a second cross-sectional survey and repeated the ocular examination and obtained conjunctival swabs from these households one year after MDA (n = 1029). RESULTS: Pre-MDA TF1-9 was 22.0% (136/618). Overall Ct infection prevalence (CtI) was 18.6% (25.4% in 1-9 year olds). Post-MDA (estimated coverage 70%), TF1-9 and CtI were significantly reduced (7.4% (29/394, P < 0.001) and 3.3% (34/1029, P < 0.001) (6.6% in 1-9 year olds, P < 0.001), respectively. Median ocular Ct load was reduced from 2038 to 384 copies/swab (P < 0.001). Following MDA cases of Ct infection were highly clustered (Moran's I 0.27, P < 0.001), with fewer clusters of Ct infection overall, fewer clusters of cases with high load infections and less severe disease. CONCLUSIONS: Despite a significant reduction in the number of clusters of Ct infection, mean Ct load, disease severity and presence of clusters of cases of high load Ct infection suggesting the beginning of trachoma control in isolated island communities, following a single round of MDA we demonstrate that transmission is still ongoing. These detailed data are useful in understanding the epidemiology of ocular Ct infection in the context of MDA and the tools employed may have utility in determining trachoma elimination and surveillance activities in similar settings

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

The conjunctival microbiome in health and trachomatous disease: a case control study.

BACKGROUND: Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection. METHODS: We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project. RESULTS: The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only. CONCLUSIONS: Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown

Systematic review of prognostic models in traumatic brain injury

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability world-wide. The ability to accurately predict patient outcome after TBI has an important role in clinical practice and research. Prognostic models are statistical models that combine two or more items of patient data to predict clinical outcome. They may improve predictions in TBI patients. Multiple prognostic models for TBI have accumulated for decades but none of them is widely used in clinical practice. The objective of this systematic review is to critically assess existing prognostic models for TBI METHODS: Studies that combine at least two variables to predict any outcome in patients with TBI were searched in PUBMED and EMBASE. Two reviewers independently examined titles, abstracts and assessed whether each met the pre-defined inclusion criteria. RESULTS: A total of 53 reports including 102 models were identified. Almost half (47%) were derived from adult patients. Three quarters of the models included less than 500 patients. Most of the models (93%) were from high income countries populations. Logistic regression was the most common analytical strategy to derived models (47%). In relation to the quality of the derivation models (n:66), only 15% reported less than 10% pf loss to follow-up, 68% did not justify the rationale to include the predictors, 11% conducted an external validation and only 19% of the logistic models presented the results in a clinically user-friendly way CONCLUSION: Prognostic models are frequently published but they are developed from small samples of patients, their methodological quality is poor and they are rarely validated on external populations. Furthermore, they are not clinically practical as they are not presented to physicians in a user-friendly way. Finally because only a few are developed using populations from low and middle income countries, where most of trauma occurs, the generalizability to these setting is limited

Serial optical coherence microscopy for label-free volumetric histopathology

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents

Rectification of electronic heat current by a hybrid thermal diode

We report the realization of an ultra-efficient low-temperature hybrid heat current rectifier, thermal counterpart of the well-known electric diode. Our design is based on a tunnel junction between two different elements: a normal metal and a superconducting island. Electronic heat current asymmetry in the structure arises from large mismatch between the thermal properties of these two. We demonstrate experimentally temperature differences exceeding $60$ mK between the forward and reverse thermal bias configurations. Our device offers a remarkably large heat rectification ratio up to $\sim 140$ and allows its prompt implementation in true solid-state thermal nanocircuits and general-purpose electronic applications requiring energy harvesting or thermal management and isolation at the nanoscale.Comment: 8 pages, 6 color figure