A mechanism for morphogen-controlled domain growth

Many developmental systems are organised via the action of graded distributions of morphogens. In the Drosophila wing disc, for example, recent experimental evidence has shown that graded expression of the morphogen Dpp controls cell proliferation and hence disc growth. Our goal is to explore a simple model for regulation of wing growth via the Dpp gradient: we use a system of reaction-diffusion equations to model the dynamics of Dpp and its receptor Tkv, with advection arising as a result of the flow generated by cell proliferation. We analyse the model both numerically and analytically, showing that uniform domain growth across the disc produces an exponentially growing wing disc

A Model for the Analysis of Caries Occurrence in Primary Molar Tooth Surfaces

Recently methods of caries quantification in the primary dentition have moved away from summary ‘whole mouth’ measures at the individual level to methods based on generalised linear modelling (GLM) approaches or survival analysis approaches. However, GLM approaches based on logistic transformation fail to take into account the time-dependent process of tooth/surface survival to caries. There may also be practical difficulties associated with casting parametric survival-based approaches in a complex multilevel hierarchy and the selection of an optimal survival distribution, while non-parametric survival methods are not generally suitable for the assessment of supplementary information recorded on study participants. In the current investigation, a hybrid semi-parametric approach comprising elements of survival-based and GLM methodologies suitable for modelling of caries occurrence within fixed time periods is assessed, using an illustrative multilevel data set of caries occurrence in primary molars from a cohort study, with clustering of data assumed to occur at surface and tooth levels. Inferences of parameter significance were found to be consistent with previous parametric survival-based analyses of the same data set, with gender, socio-economic status, fluoridation status, tooth location, surface type and fluoridation status-surface type interaction significantly associated with caries occurrence. The appropriateness of the hierarchical structure facilitated by the hybrid approach was also confirmed. Hence the hybrid approach is proposed as a more appropriate alternative to primary caries modelling than non-parametric survival methods or other GLM-based models, and as a practical alternative to more rigorous survival-based methods unlikely to be fully accessible to most researchers

Magnetic properties of Ni2.18Mn0.82Ga Heusler alloys with a coupled magnetostructural transition

Polycrystalline Ni2.18Mn0.82Ga Heusler alloys with a coupled magnetostructural transition are studied by differential scanning calorimetry, magnetic and resistivity measurements. Coupling of the magnetic and structural subsystems results in unusual magnetic features of the alloy. These uncommon magnetic properties of Ni2.18Mn0.82Ga are attributed to the first-order structural transition from a tetragonal ferromagnetic to a cubic paramagnetic phase.Comment: 4 pages, 4 figures, revtex

Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment

Background: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. Conclusions: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis

Protocol for a Randomised controlled trial to Evaluate the effectiveness and cost benefit of prescribing high dose FLuoride toothpaste in preventing and treating dEntal Caries in high-risk older adulTs (reflect trial)

Background Dental caries in the expanding elderly, predominantly-dentate population is an emerging public health concern. Elderly individuals with heavily restored dentitions represent a clinical challenge and significant financial burden for healthcare systems, especially when their physical and cognitive abilities are in decline. Prescription of higher concentration fluoride toothpaste to prevent caries in older populations is expanding in the UK, significantly increasing costs for the National Health Services (NHS) but the effectiveness and cost benefit of this intervention are uncertain. The Reflect trial will evaluate the effectiveness and cost benefit of General Dental Practitioner (GDP) prescribing of 5000ppm fluoride toothpaste and usual care compared to usual care alone in individuals 50years and over with high-risk of caries.Methods/designA pragmatic, open-label, randomised controlled trial involving adults aged 50years and above attending NHS dental practices identified by their dentist as having high risk of dental caries. Participants will be randomised to prescription of 5000ppm fluoride toothpaste (frequency, amount and duration decided by GDP) and usual care only. 1200 participants will be recruited from approximately 60 dental practices in England, Scotland and Northern Ireland and followed up for 3years. The primary outcome will be the proportion of participants receiving any dental treatment due to caries. Secondary outcomes will include coronal and root caries increments measured by independent, blinded examiners, patient reported quality of life measures, and economic outcomes; NHS and patient perspective costs, willingness to pay, net benefit (analysed over the trial follow-up period and modelled lifetime horizon). A parallel qualitative study will investigate GDPs' practises of and beliefs about prescribing the toothpaste and patients' beliefs and experiences of the toothpaste and perceived impacts on their oral health-related behaviours.DiscussionThe Reflect trial will provide valuable information to patients, policy makers and clinicians on the costs and benefits of an expensive, but evidence-deficient caries prevention intervention delivered to older adults in general dental practice.Trial registrationISRCTN: 2017-002402-13 registered 02/06/2017, first participant recruited 03/05/2018.Ethics Reference No: 17/NE/0329/233335.Funding Body: Health Technology Assessment funding stream of National Institute for Health Research.Funder number: HTA project 16/23/01.Trial Sponsor: Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL.The Trial was prospectively registered

'Support our networking and help us belong!': listening to beginning secondary school science teachers

This study, drawing on the voice of beginning teachers, seeks to illuminate their experiences of building professional relationships as they become part of the teaching profession. A networking perspective was taken to expose and explore the use of others during the first three years of a teacher’s workplace experience. Three case studies, set within a wider sample of 11 secondary school science teachers leaving one UK university’s PostGraduate Certificate in Education, were studied. The project set out to determine the nature of the networks used by teachers in terms of both how they were being used for their own professional development and perceptions of how they were being used by others in school. Affordances and barriers to networking were explored using notions of identity formation through social participation. The focus of the paper is on how the teachers used others to help shape their sense of belonging to this, their new workplace. The paper develops ideas from network theories to argue that membership of the communities are a subset of the professional inter‐relationships teachers utilise for their professional development. During their first year of teaching, eight teachers were interviewed, completing 13 semi‐structured interviews. This was supplemented in Year 2 by a questionnaire survey of their experiences. In the third year of the programme, 11 teachers (including the original sample of eight) were surveyed using a network mapping tool in which they represented their communications with people, groups and resources. Finally, three of the teachers (common to both samples) were then interviewed specifically about their networking practices and experiences using the generation of their network map as a stimulated recall focus. The implications of the analysis of these accounts are that these beginning teachers did not perceive of themselves wholly as novices and that their personal aspirations to increase participation in practical science, develop a career or work for pupils holistically did not always sit comfortably with the school communities into which they were being accommodated. While highlighting the importance of trust and respect in establishing relationships, these teachers’ accounts highlight the importance of finding ‘peers’ from whom they can find support and with whom they can reflect and potentially collaborate towards developing practice. They also raise questions about who these ‘peers’ might be and where they might be found

A Computational Clonal Analysis of the Developing Mouse Limb Bud

A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis

Multivariable association discovery in population-scale meta-omics studies.

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2\u27s linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles