Setting the agenda for dental education in Scotland: a priority setting exercise including multiple stakehiolders

Introduction The Scottish Oral Health Research Collaboration identified dental education research (DER) as a key strand of their strategy,(1) leading to the formation of the Dental Education Research Group. The starting point for this group was to understand various stakeholders’ perceptions of research priorities, yet no existing studies were found. The aim of the current study was to identify DER priorities for Scotland in the next 3-5 years. Methods The study utilised a similar methodology to that of Dennis et al,(2) in medical education. Data were collected sequentially using two online questionnaires with multiple dental stakeholders represented at undergraduate and postgraduate levels across urban and rural Scotland. 85 participants completed questionnaire 1 (qualitative) and 649 participants completed questionnaire 2 (quantitative). Qualitative and quantitative data analysis approaches were used. Results Of the 24 priorities identified, the top priorities were: role of assessments in identifying competence; undergraduate curriculum prepares for practice; and promoting teamwork within the dental team. Following factor analysis, the priorities loaded on four factors: teamwork and professionalism, measuring and enhancing performance, personal and professional development challenges, and curriculum integration and innovation. The top barriers were lack of time, funding, staff motivation, valuing of DER, and resources/ infrastructure. Discussion There were many similarities between the identified priorities for dental and medical education research2, but also some notable differences, which will be discussed. Overwhelmingly, the identified priorities in dentistry related to fitness for practice and robust assessment practices. Take home message Priority setting exercises with multiple stakeholders are an important first step in developing a national research strategy. References 1. Bagg J, Macpherson L, Mossey P, Rennie J, Saunders B, Taylor M (2010) Strategy for Oral Health Research in Scotland. Edinburgh: The Scottish Government. 2. Dennis A A, Cleland J A, Johnston P, Ker JS, Lough, M Rees CE (2014) Exploring stakeholders’ views of medical education research priorities: a national study. Medical Education, 48(11): 1078-1091.

Planet formation in a triple stellar system: implications of the third star's orbital inclination

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions.

To ensure efficient energy supply to the high demanding brain, nutrients are transported into brain cells via specific glucose (GLUT) and monocarboxylate transporters (MCT). Mitochondrial dysfunction and altered glucose metabolism are thought to play an important role in the progression of neurodegenerative diseases, including multiple sclerosis (MS). Here, we investigated the cellular localization of key GLUT and MCT proteins in human brain tissue of non-neurological controls and MS patients. We show that in control brain tissue GLUT and MCT proteins were abundantly expressed in a variety of central nervous system cells, particularly in microglia and endothelial cells. In active MS lesions, GLUTs and MCTs were highly expressed in infiltrating leukocytes and reactive astrocytes. Astrocytes manifest increased MCT1 staining and maintain GLUT expression in inactive lesions, whereas demyelinated axons exhibit significantly reduced GLUT3 and MCT2 immunoreactivity in inactive lesions. Finally, we demonstrated that the co-transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), an important protein involved in energy metabolism, is highly expressed in reactive astrocytes in active MS lesions. Overexpression of PGC-1α in astrocyte-like cells resulted in increased production of several GLUT and MCT proteins. In conclusion, we provide for the first time a comprehensive overview of key nutrient transporters in white matter brain samples. Moreover, our data demonstrate an altered expression of these nutrient transporters in MS brain tissue, including a marked reduction of axonal GLUT3 and MCT2 expression in chronic lesions, which may impede efficient nutrient supply to the hypoxic demyelinated axons thereby contributing to the ongoing neurodegeneration in MS. GLIA 2014;62:1125-1141.

Multiple introductions boosted genetic diversity in the invasive range of black cherry (Prunus serotina; Rosaceae).

BACKGROUND AND AIMS: Black cherry (Prunus serotina) is a North American tree that is rapidly invading European forests. This species was introduced first as an ornamental plant, then it was massively planted by foresters in many countries, but its origins and the process of invasion remain poorly documented. Based on a genetic survey of both native and invasive ranges, the invasion history of black cherry was investigated by identifying putative source populations and then assessing the importance of multiple introductions on the maintenance of gene diversity. METHODS: Genetic variability and structure of 23 populations from the invasive range and 22 populations from the native range were analysed using eight nuclear microsatellite loci and five chloroplast DNA regions. KEY RESULTS: Chloroplast DNA diversity suggests there were multiple introductions from a single geographic region (the north-eastern United States). A low reduction of genetic diversity was observed in the invasive range for both nuclear and plastid genomes. High propagule pressure including both the size and number of introductions shaped the genetic structure in Europe and boosted genetic diversity. Populations from Denmark, The Netherlands, Belgium and Germany showed high genetic diversity and low differentiation among populations, supporting the hypothesis that numerous introduction events, including multiple individuals and exchanges between sites, have taken place during two centuries of plantation. CONCLUSIONS: This study postulates that the invasive black cherry has originated from east of the Appalachian Mountains (mainly the Allegheny plateau) and its invasiveness in north-western Europe is mainly due to multiple introductions containing high numbers of individuals.

Interleukin-15 in the pathogenesis of multiple sclerosis and its animal models

L'interleukine-15 (IL-15) contribue au développement et à l’activation des lymphocytes T CD8, des cellules immunes qui ont été impliquées dans plusieurs maladies auto-immunes telle la sclérose en plaques. Des niveaux élevés de l'IL-15 ont été trouvés chez les patients atteints de cette maladie comparativement aux témoins, mais aucune étude n'a examiné les effets de tels niveaux élevés sur les lymphocytes T CD8. Les objectifs de notre étude étaient 1- de caractériser l’expression de l'IL-15 par des lymphocytes B humains et de déterminer ses effets sur les fonctions des lymphocytes T CD8, et 2- d’évaluer l'expression in vivo de l'IL-15 dans des modèles murins de la sclérose en plaques. Nous avons établi que les cellules B humaines augmentaient leur expression de l'IL-15 suite à une stimulation via le CD40. De plus, les fonctions effectrices des lymphocytes T CD8 ont été significativement augmentées lors des co-cultures avec des cellules B alloréactives exprimant l'IL-15. Dans les modèles murins de la sclérose en plaques, nous avons détecté au sein du système nerveux central des cellules immunes exprimant l’IL-15 ainsi que des cellules T CD8 exprimant le récepteur pour cette cytokine à différents stades de la maladie. Nous avons démontré que les cellules B modulent des réponses des lymphocytes T CD8 via l’IL-15, ce qui suggère un rôle pour les cellules B dans la pathogenèse de la sclérose en plaques. Nous avons aussi mis en évidence la présence de cellules exprimant l’IL-15 dans le système nerveux central dans des modèles murins de cette maladie.

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma - The DD protocol

Context and Objective: Lipasomial daunorubicin has been used to treat hematological malignancies, including multiple myelomo (MM). The goal was to evaluate efficacy, side-effects and toxicity of liposomal daunorubicin and dexamethasone (DD Protocol). Design and Setting: Prospective study of Sírio-Libonês, São Camilo, Brasil and Alemão Oswaldo Cruz hospitals. Methods: Twenty consecutive patients with active MM received four cycles of liposomal daunorubicin intravenously for two hours (25-30 mg/m 2/day) on three consecutive days per month, with oral dexamethasone, (10 mg every six hours) on four consecutive days three times a month. Results: The male/female ratio was 1:1 and median age 60. Nine patients were stage IIA, ten IIIA and one IIIB. The median from diagnosis to starting DD was 13 months. All patients received four cycles, except one. Fifteen had already received chemotherapy before DD. Responses of > 50% reduction in serum monoclonal paraprotein were observed in six patients after first cycle (30%), six after second (30%) and four after third (20%), while four (20%) did not obtain this. Initially, 17 patients (85%) had anemia: 12 (70%) achieved correction. Progressive disease was observed in three patients (15%), while one had minimal response, four (20%) partial and 12 (60%) complete. Hemotologlical toxicity was acceptable: three patients (15%) had neutrophils < 1,000/mm 3; none had thrombocyfopenia. Gastrointestinal toxicity was mild: nausea (10%), anorexio (15%) and no vomiting. Conclusions: This treatment has mild toxicity and good response rate. It may therefore be feasible before autologous bone marraw transplantation.

A new method for conservation planning for the persistence of multiple species

Although the aim of conservation planning is the persistence of biodiversity, current methods trade-off ecological realism at a species level in favour of including multiple species and landscape features. For conservation planning to be relevant, the impact of landscape configuration on population processes and the viability of species needs to be considered. We present a novel method for selecting reserve systems that maximize persistence across multiple species, subject to a conservation budget. We use a spatially explicit metapopulation model to estimate extinction risk, a function of the ecology of the species and the amount, quality and configuration of habitat. We compare our new method with more traditional, area-based reserve selection methods, using a ten-species case study, and find that the expected loss of species is reduced 20-fold. Unlike previous methods, we avoid designating arbitrary weightings between reserve size and configuration; rather, our method is based on population processes and is grounded in ecological theory.

Immunopathology and Pathophysiology of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS), and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (Raine, 1984). EAE can be induced by inoculation with whole CNS tissue, purified myelin basic protein (MBP) or myelin proteolipid protein (PLP), together with adjuvants. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens. EAE may have either an acute or a chronic relapsing course. Acute EAE closely resembles the human disease acute disseminated encephalomyelitis, while chronic relapsing EAE resembles multiple sclerosis. EAE is also the prototype for T-cell-mediated autoimmune disease in general. This chapter will focus on the immunopathology and pathophysiology of EAE, which are the subjects of investigation in my laboratory.

Inter-subband redundancy prediction using neural network for video coding

High performance video codec is mandatory for multimedia applications such as video-on-demand and video conferencing. Recent research has proposed numerous video coding techniques to meet the requirement in bandwidth, delay, loss and Quality-of-Service (QoS). In this paper, we present our investigations on inter-subband self-similarity within the wavelet-decomposed video frames using neural networks, and study the performance of applying the spatial network model to all video frames over time. The goal of our proposed method is to restore the highest perceptual quality for video transmitted over a highly congested network. Our contributions in this paper are: (1) A new coding model with neural network based, inter-subband redundancy (ISR) prediction for video coding using wavelet (2) The performance of 1D and 2D ISR prediction, including multiple levels of wavelet decompositions. Our result shows a short-term quality enhancement may be obtained using both 1D and 2D ISR prediction.

SDAR: a package for plotting and analyzing stratigraphy data in R

Stratigraphic Columns (SC) are the most useful and common ways to represent the eld descriptions (e.g., grain size, thickness of rock packages, and fossil and lithological components) of rock sequences and well logs. In these representations the width of SC vary according to the grain size (i.e., the wider the strata, the coarser the rocks (Miall 1990; Tucker 2011)), and the thickness of each layer is represented at the vertical axis of the diagram. Typically these representations are drawn 'manually' using vector graphic editors (e.g., Adobe Illustrator®, CorelDRAW®, Inskape). Nowadays there are various software which automatically plot SCs, but there are not versatile open-source tools and it is very di cult to both store and analyse stratigraphic information. This document presents Stratigraphic Data Analysis in R (SDAR), an analytical package1 designed for both plotting and facilitate the analysis of Stratigraphic Data in R (R Core Team 2014). SDAR, uses simple stratigraphic data and takes advantage of the exible plotting tools available in R to produce detailed SCs. The main bene ts of SDAR are: (i) used to generate accurate and complete SC plot including multiple features (e.g., sedimentary structures, samples, fossil content, color, structural data, contacts between beds), (ii) developed in a free software environment for statistical computing and graphics, (iii) run on a wide variety of platforms (i.e., UNIX, Windows, and MacOS), (iv) both plotting and analysing functions can be executed directly on R's command-line interface (CLI), consequently this feature enables users to integrate SDAR's functions with several others add-on packages available for R from The Comprehensive R Archive Network (CRAN).

NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.

We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.

Minocycline Promotes Remyelination in an In Vitro Model of Demyelination

Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated by agents such as interferon-g (IFN-g) and lipopolysaccharide (LPS). Aggregating brain cultures exposed to a repeated treatment (3 fold) with IFN-g (50 U/ml) and LPS (5 ug/ml) were used as an in vitro model of demyelination. Demyelination could be due to either the direct effect of IFN-g and LPS on oligodendrocytes or the IFN-g and LPS-induced inflammatory response. We investigated the involvement of microglial reactivity in demylination and remyelination by using minocycline, an antibiotic known to block microglial reactivity. Changes in myelination were examined by measuring the expression of myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) at the mRNA level by quantitative RT-PCR and at the protein level by Western blotting and immunohistochemistry. To evaluate brain inflammatory reactions, microglia were stained with isolectin B4 (IB4), quantitative RT-PCR was used to determine the expression of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and inducible NO synthase (iNOS). The repeated treatment with IFN-g and LPS caused demyelination, as indicated by a decrease in MBP and MOG expression. It also activated microglial cells, and up-regulated TNF-a, IL-6, and iNOS expression. Although minocycline did not affect the IFN-g- and LPS-induced upregulation of TNF-a, IL-6, it decreased the number of IB4-labeled microglial cells. Furthermore, minocycline did not prevent demyelination, whereas it strongly increased MBP expression one week after the end of the demyelinating treatment. In conclusion, the present results show that minocycline promoted remyelination after IFN-g- and LPS-induced demyelination, presumably due to its effects on microglial cells.

Material and Construction Optimization for Prevention of Premature Pavement Distress in PCC Pavements, September 2004

The chemistry of today’s concrete mixture designs is complicated by many variables, including multiple sources of aggregate and cements and a plethora of sometimes incompatible mineral and chemical admixtures. Concrete paving has undergone significant changes in recent years as new materials have been introduced into concrete mixtures. Supplementary cementitious materials such as fly ash and ground granulated blast furnace slag are now regularly used. In addition, many new admixtures that were not even available a few years ago now have widespread usage. Adding to the complexity are construction variables such as weather, mix delivery times, finishing practices, and pavement opening schedules. Mixture materials, mix design, and pavement construction are not isolated steps in the concrete paving process. Each affects and is affected by the other in ways that determine overall pavement quality and long-term performance. Equipment and procedures commonly used to test concrete materials and concrete pavements have not changed in decades, leaving serious gaps in our ability to understand and control the factors that determine concrete durability. The concrete paving community needs tests that will adequately characterize the materials, predict interactions, and monitor the properties of the concrete.

OpenFluDB, a database for human and animal influenza virus.

Although research on influenza lasted for more than 100 years, it is still one of the most prominent diseases causing half a million human deaths every year. With the recent observation of new highly pathogenic H5N1 and H7N7 strains, and the appearance of the influenza pandemic caused by the H1N1 swine-like lineage, a collaborative effort to share observations on the evolution of this virus in both animals and humans has been established. The OpenFlu database (OpenFluDB) is a part of this collaborative effort. It contains genomic and protein sequences, as well as epidemiological data from more than 27,000 isolates. The isolate annotations include virus type, host, geographical location and experimentally tested antiviral resistance. Putative enhanced pathogenicity as well as human adaptation propensity are computed from protein sequences. Each virus isolate can be associated with the laboratories that collected, sequenced and submitted it. Several analysis tools including multiple sequence alignment, phylogenetic analysis and sequence similarity maps enable rapid and efficient mining. The contents of OpenFluDB are supplied by direct user submission, as well as by a daily automatic procedure importing data from public repositories. Additionally, a simple mechanism facilitates the export of OpenFluDB records to GenBank. This resource has been successfully used to rapidly and widely distribute the sequences collected during the recent human swine flu outbreak and also as an exchange platform during the vaccine selection procedure. Database URL: http://openflu.vital-it.ch.

Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination.

BACKGROUND: Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Peroxisome proliferator-associated receptor (PPAR) pathways are involved in the control of the inflammatory processes, and PPAR-beta seems to play an important role in the regulation of central inflammation. In addition, PPAR-beta agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-beta agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-gamma and LPS. METHODS: Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-gamma and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG). The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), inducible NO synthase (i-NOS), PPAR-beta, PPAR-gamma, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and high molecular weight neurofilament protein (NF-H). GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4) and ED1 labeling. RESULTS: GW 501516 decreased the IFN-gamma-induced up-regulation of TNF-alpha and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-beta agonist. However, it increased IL-6 m-RNA expression. In demyelinating cultures, reactivity of both microglial cells and astrocytes was observed, while the expression of the inflammatory cytokines and iNOS remained unaffected. Furthermore, GW 501516 did not protect against the demyelination-induced changes in gene expression. CONCLUSION: Although GW 501516 showed anti-inflammatory activity, it did not protect against antibody-mediated demyelination. This suggests that the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes.