Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Integrating Intangible Cultural Heritage elements and learning strategy : a case study

Tanzania has a rich and diverse cultural history based on community cultural life. However, at present, young people have limited opportunity to exploit this richness of creative expressions and engage in creative jobs as their future career. Hence, the significant challenge remains: how to integrate Intangible cultural heritage elements and learning strategy as a means of promoting creative jobs for youth. This paper presents a case study on 'Strategies for youth employment in Tanzania: A creative industries approach'. The case study employed mixed methods incorporating questionnaires, interviews and focus groups and was held in Dar-Es-Salaam, Mwanza, Dodoma, Lindi and Morogoro from July to October, 2012. This paper discusses some of the issues and argues that there is no virtual utilization of the intangible cultural heritage knowledge and skills in 'putting education to work' (UNESCO, 2012) for the better prospects of youth. Although the discussion is specific to Tanzania, the case may also apply to other developing countries.

The pre-socialization of future journalists

While the role of university journalism education in the professionalization of journalists has been extensively debated, systematic and comparative studies of journalism students are still scarce. This paper reports the findings from a comparative study of journalism students in seven countries: Australia, Brazil, Chile, Mexico, Spain, Switzerland, and the United States. The data show a number of similarities, but also important differences between pre-professional cultures in journalism around the world. The findings are in line with recent conceptualizations of media systems, although some variations and particularities are observed at the country level. While students in all countries reject a loyal approach and favor a citizen-oriented role, they also do so to different extents. Brazilian and Chilean students believe in the citizen-oriented and watchdog roles, whereas their counterparts in Australia, Switzerland, and the United States favor the consumer-oriented approach to a greater extent. Mexican and Spanish students, on the other hand, while supporting the citizen-oriented role, reject the loyal role comparatively less than the rest of the countries.

A nonlinear observer for estimating transverse stability parameters of marine surface vessels

This paper presents a nonlinear observer for estimating parameters associated with the restoring term of a roll motion model of a marine vessel in longitudinal waves. Changes in restoring, also referred to as transverse stability, can be the result of changes in the vessel's centre of gravity due to, for example, water on deck and also in changes in the buoyancy triggered by variations in the water-plane area produced by longitudinal waves -- propagating along the fore-aft direction along the hull. These variations in the restoring can change dramatically the dynamics of the roll motion leading to dangerous resonance. Therefore, it is of interest to estimate and detect such changes.

Some Reflections on the Emergence of Multimodal Assemblages of Meaning

In this commentary I reflect upon the conceptualisation of human meaning-making, utilised in the two target articles, that relies heavily on speech as the main mode of semiosis and considers time only in its chronological form. Instead I argue that human existence is embodied and lived through multiple modalities, and involves not only sequential experience of time, but also experience of emergence. In order to move towards a conception of meaning-making that takes this into account, I introduce the social-semiotic theory of multimodality (Kress 2010) and discuss notions of ‘real duration’ (Bergson 1907/1998) and ‘lived time’ (Martin-Vallas 2009). I argue that dialogical (idiographic) researchers need to develop analytic and methodological tools that allow exploring the emergence of multimodal assemblages of meaning in addition to trying to avoid the monologisation of complex dynamic dialogical phenomena.

Managing and sharing health data through information accountability protocols

Concerns over the security and privacy of patient information are one of the biggest hindrances to sharing health information and the wide adoption of eHealth systems. At present, there are competing requirements between healthcare consumers' (i.e. patients) requirements and healthcare professionals' (HCP) requirements. While consumers want control over their information, healthcare professionals want access to as much information as required in order to make well-informed decisions and provide quality care. In order to balance these requirements, the use of an Information Accountability Framework devised for eHealth systems has been proposed. In this paper, we take a step closer to the adoption of the Information Accountability protocols and demonstrate their functionality through an implementation in FluxMED, a customisable EHR system.

Medical Data Access Accountability in EHR Systems, A Practical Perspective

The world has experienced a large increase in the amount of available data. Therefore, it requires better and more specialized tools for data storage and retrieval and information privacy. Recently Electronic Health Record (EHR) Systems have emerged to fulfill this need in health systems. They play an important role in medicine by granting access to information that can be used in medical diagnosis. Traditional systems have a focus on the storage and retrieval of this information, usually leaving issues related to privacy in the background. Doctors and patients may have different objectives when using an EHR system: patients try to restrict sensible information in their medical records to avoid misuse information while doctors want to see as much information as possible to ensure a correct diagnosis. One solution to this dilemma is the Accountable e-Health model, an access protocol model based in the Information Accountability Protocol. In this model patients are warned when doctors access their restricted data. They also enable a non-restrictive access for authenticated doctors. In this work we use FluxMED, an EHR system, and augment it with aspects of the Information Accountability Protocol to address these issues. The Implementation of the Information Accountability Framework (IAF) in FluxMED provides ways for both patients and physicians to have their privacy and access needs achieved. Issues related to storage and data security are secured by FluxMED, which contains mechanisms to ensure security and data integrity. The effort required to develop a platform for the management of medical information is mitigated by the FluxMED's workflow-based architecture: the system is flexible enough to allow the type and amount of information being altered without the need to change in your source code.

Indigenous cultural landscapes: Equitably defining the 'authenticity' of the intangible

Over hundreds of generations, indigenous groups around the world have passed down their traditional landscape associations, a number of which are intangible and therefore unquantifiable. Yet, these associative relationships with nature have been, and continue to be, pivotal in cultural evolution. Determining the authenticity of intangible landscape associations has caused much controversy, and in recent decades, indigenous groups have begun seeking protection of their places of significance. In response, the United Nations Educational, Scientific and Cultural Organisation (UNESCO) World Heritage Committee (WHC) developed a criterion that intended to assist in the identification and protection of cultural landscapes. The WHC has therefore become the global authority responsible for determining the authenticity of cultural landscapes, including those with intangible associations rather than material cultural evidence. However, even with the support of the United Nations, UNESCO and the WHC, it is unlikely that every tangible cultural landscape will be sufficiently recognised and protected. Therefore, this research paper explores the effectiveness of current approaches to gauging authenticity in instances where multiple landscapes are valued according to similar characteristics. Further, this work studies the inherent relationship between the indigenous Maori population of the South Island of New Zealand, in particular Kai Tahi peoples, and their significant landscape features, as a means of considering the breadth and depth of historic intangible associations. In light of these findings, this research challenges the appropriateness of the term 'authenticity' when analysing not only the subjective, but more pressingly, the intangible. It therefore questions the role of empirical data in demonstrating authenticity, while recognising that a prolific list of such intangible cultural landscapes has the potential to diminish integrity. This, this paper addresses an urgent need for increased social research in this area, namely in identifying cultural landscape protection methods that empower all local indigenous communities, not just those which are the most critically acclaimed.

Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

Summary We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

Programming rumen bacterial communities in newborn Merino lambs

Establishment of the rumen microbiome can be affected by both early-life dietary measures and rumen microbial inoculation. This study used a 2 × 3 factorial design to evaluate the effects of inclusion of dietary fat type and the effects of rumen inoculum from different sources on ruminal bacterial communities present in early stages of the lambs’ life. Two different diets were fed ad libitum to 36 pregnant ewes (and their lambs) from 1 month pre-lambing until weaning. Diets consisted of chaffed lucerne and cereal hay and 4% molasses, with either 4% distilled coconut oil (CO) provided as a source of rumen-active fat or 4% Megalac® provided as a source of rumen-protected fat (PF). One of three inoculums was introduced orally to all lambs, being either (1) rumen fluid from donor ewes fed the PF diet; (2) rumen fluid from donor ewes fed CO; or (3) a control treatment of MilliQ-water. After weaning at 3 months of age, each of the six lamb treatment groups were grazed in spatially separated paddocks. Rumen bacterial populations of ewes and lambs were characterised using 454 amplicon pyrosequencing of the V3/V4 regions of the 16S rRNA gene. Species richness and biodiversity of the bacterial communities were found to be affected by the diet in ewes and lambs and by inoculation treatment of the lambs. Principal coordinate analysis and analysis of similarity (ANOSIM) showed between diet differences in bacterial community groups existed in ewes and differential bacterial clusters occurred in lambs due to both diet and neonatal inoculation. Diet and rumen inoculation acted together to clearly differentiate the bacterial communities through to weaning, however the microbiome effects of these initial early life interventions diminished with time so that rumen bacterial communities showed greater similarity 2 months after weaning. These results demonstrate that ruminal bacterial communities of newborn lambs can be altered by modifying the diet of their mothers. Moreover, the rumen microbiome of lambs can be changed by diet while they are suckling or by inoculating their rumen, and resulting changes in the rumen bacterial microbiome can persist beyond weaning.

TiO2-RGO hybrid nanomaterials for enhanced water splitting reaction

The production of H-2 via photocatalytic water splitting reaction has attracted a great attention as a clean and renewable energy for next generation. Despite tremendous efforts, the present challenge for materials scientist is to develop highly active photo catalysts for splitting of water at low cost. This article reports the synthesis of TiO2-reduced graphene oxide hybrid nanomaterials through ionothermal method using functionalized ionic liquid for the enhanced hydrogen generation via water splitting reaction. The structural and morphological properties of the samples were investigated by XFtD, Raman spectroscopy, TG-DTA, UV-vis spectroscopy and TEM. A substantial increase of H-2 evolution was observed for TiO2-reduced graphene oxide hybrid nanomaterials. This is due to the high migration efficiency of photo-induced electrons and the inhibition of charge carrier recombination due to the electronic interaction between TiO2 and reduced graphene oxide. i.e, reduced graphene oxide acts as an electron-acceptor which effectively hinders the electron hole pair recombination of TiO2. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Evaluación del comportamiento de falso roble (Tabebuia rosea (Bertol.) DC.), Genízaro (Pithecellobium saman (Jacq.) Benth.) y Guanacaste negro (Enterolobium cyclocarpum (Jacq.) Griseb.) en ensayo de germinación y sembrados en dos tipos de sustrato orgánico

Las etapas de este trabajo de investigación se llevaron a cabo en las instalaciones del invernadero y vivero de la Universidad Nacional Agraria, ubicada a la altura del kilómetro 12 carretera norte en la ciudad de Managua. Se realizó un ensayo de germinación con semillas falso roble Tabebuia rosea (Bertol.) DC., genízaro Phitecellobium saman (Jacq.) Benth. y guanacaste negro Enterolobium cyclocarpum (Jacq.) Griseb., para cuantificar el porcentaje, energía y valor de la germinación aplicando tratamientos pre germinativos. Posteriormente, en vivero, se establecieron dichas especies en un diseño de bloques completos al azar con tres bloques por especie, tres tratamientos por bloque y noventa repeticiones por tratamiento, realizando un ANDEVA y aplicando una prueba de separación de medias. Las variables evaluadas en el ANDEVA fueron altura total y diámetro basal. Separadamente se evaluó la mortalidad y sobrevivencia de las plantas en el vivero. El tratamiento pre germinativo que dio mejores resultados fue el rompimiento de la testa en el extremo donde se encuentra el micrópilo, con porcentajes de germinación superiores al 90%. No se encontraron diferencias significativas entre tratamientos, por lo cual no hubo efecto de los sustratos sobre los incrementos de las plantas de genízaro Phitecellobium saman (Jacq.) Benth. y se encontraron diferencias significativas entre tratamientos y variables para guanancaste negro Enterolobium cyclocarpum (Jacq.) Griseb. con los mayores incrementos en compostaje con 29,32 cm y los menores en tierra común 18,82 cm. El compostaje fue el sustrato donde ocurrió la mayor sobrevivencia de guanacaste negro Phitecellobium saman (Jacq.) Benth. con 85% y genízaro Phitecellobium saman (Jacq.) Benth. con 66%. Los valores de mortalidad fueron menores al 26% en todos los sustratos.