An atomic scale comparison of the reaction of Bioglass® in two types of simulated body fluid

A class of melt quenched silicate glasses, containing calcium, phosphorus and alkali metals, and having the ability to promote bone regeneration and to fuse to living bone, is produced commercially as Bioglass. The changes in structure associated with reacting the bioglass with a body fluid simulant (a buffered Tris(hydroxymethyl)aminomethane growth medium solution or a blood plasma-like salt simulated body fluid) at 37°C have been studied using both high energy and grazing incidence x-ray diffraction. This has corroborated the generic conclusions of earlier studies based on the use of calcia–silica sol-gel glasses whilst highlighting the important differences associated with glass composition; the results also reveal the more subtle effects on reaction rates of the choice of body fluid simulant. The results also indicate the presence of tricalcium phosphate crystallites deposited onto the surface of the glass as a precursor to the growth of hydroxyapatite, and indicates that there is some preferred orientation to their growth

The structure of calcium metaphosphate glass obtained from x-ray and neutron diffraction and reverse Monte Carlo modelling

The short range structure of (CaO)(0.5)(P2O5)(0.5) glass has been studied using x-ray and neutron diffraction and modelled using the reverse Monte Carlo method. Using this combination of techniques has allowed six interatomic correlations to be distinguished and fitted to obtain a set of bond lengths and coordination numbers that describe the structure of the glass. The glass consists of metaphosphate chains of phosphate tetrahedra and each phosphate unit has two non-bridging oxygen atoms available for coordination with Ca. The Ca-O correlation was fitted with two peaks at 2.35 and 2.86 angstrom, representing a broad distribution of bond lengths. The total Ca-O coordination is 6.9 and is consistent with distorted polyhedral units such as capped octahedra or capped trigonal prisms. It is found that most non-bridging oxygen atoms are bonded to two calcium atoms. All of these observations are consistent with Hoppe's model for phosphate glasses. Furthermore, the medium range order is revealed to consist of phosphate chains intertwined with apparently elongated clusters of Ca ions, and the Ca-O and Ca-P correlations contributed significantly to the first sharp diffraction peak in x-ray diffraction

A map of the class III region of the sheep major histocompatibilty complex

<p>Abstract</p> <p>Background</p> <p>The central, or class III, region of the major histocompatibility complex (MHC) is an important gene rich sub-region of the MHC of mammals and contains many loci implicated in disease processes and potential productivity traits. As a prelude to identifying MHC loci associated with productivity traits in sheep, we have used BAC and cosmid libraries of genomic DNA to generate a physical map of the sheep MHC class III region. This map will facilitate association studies and provide insights into the distribution of recombination events in this chromosomal segment.</p> <p>Results</p> <p>Twenty eight sheep genes were identified in 10 BAC clones which spanned approximately 700 kbp of a chromosomal region adjacent to the class I region of the sheep MHC and which therefore covers most, if not all, of the class III of the sheep MHC. The relative positions of 17 of these genes was established as well as two additional groups of genes for which the intragroup order was not known. Cosmid mapping permitted a more detailed mapping of the complement genes present in the class III and showed a local inversion (relative to humans) of one pair of the duplicated complement C4 and CYP21 loci. A panel of 26 single nucleotide polymorphisms (SNPs) was identified in 10 loci, covering ≈600 kbp of the mapped region.</p> <p>Conclusion</p> <p>This report provides a physical map covering ≈700 kbp of the class III of the sheep MHC together with a SNP panel which will facilitate disease and productivity association studies. The presence of a local inversion (relative to humans) of one pair of the duplicated C4 and CYP21 loci and a previously described dinucleotide tandem repeat locus (BfMs) has been located within an intron of the SK12VL gene.</p

Characterization of the sheep Complement Factor B gene (CFB)

The Complement Factor B gene (CFB) of the alternative complement pathway has been identified in the sheep Major Histocompatibility Complex (MHC) and its genomic sequence determined. CFB is located approximately 600bp upstream of the complement C2 gene, contains 18 exons, and manifests the domain signature characteristic of CFB protein. Thirteen single nucleotide polymorphisms were identified in merino sheep and interbreed variation was identified by comparison with International Sheep Genomics Consortium data. Two predicted non synonymous substitutions were observed and in-silico analysis indicates that these are likely to have a destabilising effect on the protein structure. Sheep and cattle CFB were compared and shown to contain a common nine nucleotide deletion in exon 18 relative to human CFB. Predicted CFB amino acid sequences for these two species contain 761 aa relative to 764 aa in the human orthologue. Sequencing of the cosmid and BAC clones used in this study permitted the relative positions of three adjacent loci to be determined and showed that the previously described microsatellite locus (BfMs) is located within SKIV2L

Clinical judgement, case complexity and symptom scores as predictors of outcome in depression: an exploratory analysis

Background: Clinical guidelines for depression in adults recommend the use of outcome measures and stepped care models in routine care. Such measures are based on symptom severity, but response to treatment is likely to also be influenced by personal and contextual factors. This observational study of a routine clinical sample sought to examine the extent to which “symptom severity measures” and “complexity measures” assess different aspects of patient experience, and how they might relate to clinical outcomes, including disengagement from treatment. Methods: Subjects with symptoms of depression (with or without comorbid anxiety) were recruited from people referred to an established Primary Care Mental Health Team using a stepped care model. Each participant completed three baseline symptom measures (the Personal Health Questionnaire (PHQ), Generalised Anxiety Disorder questionnaire (GAD) and Clinical Outcomes in Routine Evaluation (CORE-10)), and two assessments of “case complexity” (the Minnesota-Edinburgh Complexity Assessment Measure (MECAM) and a local complexity assessment). Clinician perception of likely completion of treatment and patient recovery was also assessed. Outcome measures were drop out and clinical improvement on the PHQ. Results: 298 subjects were recruited to the study, of whom 258 had a sufficient dataset available for analysis. Data showed that the three measures of symptom severity used in this study (PHQ, GAD and CORE-10) seemed to be measuring distinct characteristics from those associated with the measures of case complexity (MECAM, previous and current problem count). Higher symptom severity scores were correlated with improved outcomes at the end of treatment, but there was no association between outcome and complexity measures. Clinicians could predict participant drop-out from care with some accuracy, but had no ability to predict outcome from treatment. Conclusions: These results highlight the extent to which drop-out complicates recovery from depression with or without anxiety in real-world settings, and the need to consider other factors beyond symptom severity in planning care. The findings are discussed in relation to a growing body of literature investigating prognostic indicators in the context of models of collaborative care for depression

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals

A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression

Peer-led intervention to prevent and reduce STI transmission and improve sexual health in secondary schools (STASH): protocol for a feasibility study

Background: Young people in the UK are at highest risk of sexually transmitted infections and report higher levels of unsafe sex than any other age group. Involving peer supporters in intervention delivery is acceptable to students and effective in reducing risk behaviours via ‘diffusion of innovation’, particularly where peer supporters are influential in their networks. Informal peer-led interventions offer a useful alternative to peer-led didactic teaching, which has shown limited effects. Building on the successful ASSIST anti-smoking intervention, the ‘STis And Sexual Health’ (STASH) intervention involves identification and recruitment of the most influential students as peer supporters, training and support to these students by specialist trainers, positive sex and relationships messages, spread by peer supporters to their friendship groups in person and via social media. Methods/design: This protocol describes a feasibility trial of the STASH intervention in six schools. It builds on an earlier study phase of intervention co-development using patient and public involvement (PPI) activities, followed by a pilot of intervention components and evaluation tools in one school. Participants are fourth year (S4) students (aged 14–16) in state-funded Scottish secondary schools who have received some level of teacher-led sex education. The previous cohort of S4 students (those completing S4 in the year prior to the intervention) will serve as controls. Data will be collected from controls (month 16), baseline (month 20–21) and follow-up (month 27–30) via a web-based questionnaire, which will measure (and test the reliability of) primary outcome measures for a phase III trial (delayed initiation of/abstinence from sex and consistent condom use), secondary outcomes and mediators of sexual behaviour (including school climate and social networks). The main feasibility outcome is whether the study meets pre-set progression criteria regarding feasibility and acceptability, measured largely via a process evaluation (basic measures in all 6 schools and in-depth in 2-4 schools). An economic evaluation reporting costs alongside consequences will be conducted. Discussion: This study will inform decisions on the feasibility, design and sample size for a phase III effectiveness trial to assess whether the STASH intervention is effective in reducing the risk of sexually transmitted infections in young people

Predicting future suicidal behaviour in young adults, with different machine learning techniques: a population-based longitudinal study

Background: The predictive accuracy of suicidal behaviour has not improved over the last decades. We aimed to explore the potential of machine learning to predict future suicidal behaviour using population-based longitudinal data. Method: Baseline risk data assessed within the Scottish wellbeing study, in which 3508 young adults (18-34 years) completed a battery of psychological measures, were used to predict both suicide ideation and suicide attempts at one-year follow-up. The performance of the following algorithms was compared: regular logistic regression, K-nearest neighbors, classification tree, random forests, gradient boosting and support vector machine. Results: At one year follow up, 2428 respondents (71%) finished the second assessment. 336 respondents (14%) reported suicide ideation between baseline and follow up, and 50 (2%) reported a suicide attempt. All performance metrics were highly similar across methods. The random forest algorithm was the best algorithm to predict suicide ideation (AUC 0.83, PPV 0.52, BA 0.74) and the gradient boosting to predict suicide attempt (AUC 0.80, PPV 0.10, BA 0.69). Limitations: The number of respondents with suicidal behaviour at follow up was small. We only had data on psychological risk factors, limiting the potential of the more complex machine learning algorithms to outperform regular logistical regression. Conclusions: When applied to population-based longitudinal data containing multiple psychological measurements, machine learning techniques did not significantly improve the predictive accuracy of suicidal behavior. Adding more detailed data on for example employment, education or previous health care uptake, might result in better performance of machine learning over regular logistical regression

Identification and characterisation of ten microsatellite loci in the Noisy Scrub-bird Atrichornis clamosus using next-generation sequencing technology

The Noisy Scrub-bird is an endangered species of songbird endemic to the south coast of Western Australia that has undergone a major and prolonged population bottleneck. Using shotgun 454 next-generation DNA sequencing we have identified and characterised ten polymorphic microsatellite loci in this species. Observed allelic diversity was relatively low (2–5 alleles per locus) and significant deviations from Hardy–weinberg Equilibrium observed, although the presence of null alleles was onlypostulated for two loci. The microsatellite loci characterised in this study will be useful in a future population genetics studies in this endangered species