Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Evidence-based practice

This chapter traces the history of evidence-based practice (EBP) from its roots in evidence-based medicine to contemporary thinking about its usefulness to public health practice. It defines EBP and differentiates it from ‘evidence-based medicine’, ‘evidence-based policy’ and ‘evidence-based healthcare’. As it is important to understand the subjective nature of knowledge and the research process, this chapter describes the nature and production of knowledge. This chapter considers the necessary skills for EBP, and the processes of attaining the necessary evidence. We examine the barriers and facilitators to identifying and implementing ‘best practice’, and when EBP is appropriate to use. There is a discussion about the limitations of EBP and the use of other information sources to guide practice, and concluding information about the application of evidence to guide policy and practice.

Disease control and management

Globally, the main contributors to morbidity and mortality are chronic conditions, including cardiovascular disease and diabetes. Chronic disease is costly and partially avoidable, with around 60% of deaths and nearly 50% of the global disease burden attributable to these conditions. By 2020, chronic illnesses will likely be the leading cause of disability worldwide. Existing healthcare systems that focus on acute episodic health conditions, both national and international, cannot address the worldwide transition to chronic illness; nor are they appropriate for the ongoing care and management of those already dealing with chronic diseases. As such, chronic disease management requires integrated approaches that incorporate interventions targeted at both individuals and populations, and emphasise the shared risk factors of different conditions. International and Australian strategic planning documents articulate similar elements to manage chronic disease, including the need for aligning sectoral policies for health, forming partnerships, and engaging communities in decision-making. Infectious diseases are also a common and significant contributor to ill health throughout the world. In many countries, this impact has been minimised by the combined efforts of preventative health measures and improved treatment methods. However, in low-income countries, infectious diseases remain the dominant cause of death and disability. The World Health Organization (WHO) estimates that infectious diseases (including respiratory infections) still account for around 23% (or around 14 million) of all deaths each year, and result in over 4.6 billion episodes of diarrhoeal disease and 243 million cases of malaria each year (Lozano et al. 2012, WHO 2009). In addition to the high level of mortality, infectious diseases disable many hundreds of millions of people each year, mainly in developing countries, with the global burden of disease from infectious diseases estimated to be around 300 million DALYs (disability-adjusted life years) (WHO 2012). The aim of this chapter is to outline the impact that infectious diseases and chronic diseases have on the health of the community, describe the public health strategies used to reduce the burden of those diseases, and discuss the historic and emerging disease risks to public health. This chapter examines the comprehensive approaches implemented to prevent both chronic and infectious diseases, and to manage and care for communities with these conditions.

Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis

Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation(1). As gut-derived serotonin (GDS) inhibits bone formation(2), we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose-dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.

The last avant-garde?: Disability arts and (rethinking) mobility

Taking as its starting point a remark by Turner Prize nominee Yinka Shonibare that disability arts is “the last avant garde”, this panel focuses on the role of aesthetic experimentation in disability arts and the possible rethinking of the relationship between avant-garde aesthetic strategies and inclusive arts. Points of connection between the avant-garde and disability arts include a rejection of traditional aesthetic forms, the development of aesthetic strategies appropriate to non-normative bodies, politics and populations and the implications of these ideas for the conference themes. This panel is intended as a facilitated discussion involving researchers and artists undertaking work in this area. The panel will begin with some brief provocations reflecting on the implication of Shonibare’s comment. For example, Gerard Goggin will discuss three projects by Antoni Abad with artists and activists with disability in Barcelona, Geneva and Montreal as part of Abad’s Megaphone project, a decade-long, global digital art project. Bree Hadley will speak on performative interventions in public space, performance art, live art, activism and culture hacking by artists with disabilities, such as pwd's online performances, and artist’s performative responses to the austerity agenda in the US, UK, and Australasia. Eddie, Lachlan and Sarah will discuss ideas arising from their work on the project Beyond Access: The Creative Case for Inclusive Arts, which involved research with six Melbourne-based artists/artistic companies with disability, supported by Arts Access Victoria. Chair: Dr Eddie Paterson (School of Culture and Communication, Faculty of Arts, University of Melbourne) Dr Bree Hadley (Creative Industries, QUT) Professor Gerard Goggin (Professor of Media and Communication and ARC Future Fellow, University of Sydney) Dr Lachlan MacDowall (Head, Centre for Cultural Partnerships, University of Melbourne). Sarah Austin (PhD candidate, Theatre/Centre for Cultural Partnerships, VCA and MCM) Artists (tbc, based on existing relationships with artists developed in the Beyond Access research).

Kolmas tehtävä ja neljäs valtiomahti. Uusi yliopistolaki ja yliopiston rooli yhteiskunnassa julkisen keskustelun kohteena 2008-2009.

Tässä pro gradu -tutkielmassa tarkastellaan yliopiston yhteiskunnallista vuorovaikutusta koskevaa julkista keskustelua. Aineisto koostuu viiden levikiltään Suomen suurimpien joukkoon kuuluvan sanomalehden yliopiston yhteiskunnallista vuorovaikutusta käsittelevistä pääkirjoituksista ajalta 1.1.2008–31.12.2009. Pääkirjoituksia on aineistossa yhteensä 110. Tutkielman tarkoituksena on täydentää politiikan tutkimuksen alalla laiminlyötyä koulutuspolitiikan tutkimusta paneutuen yliopiston yhteiskunnallista roolia koskeviin merkityksiin, jotka nousivat aktiiviseen julkiseen keskusteluun yliopistolain uudistuksen myötä. Tutkimuskysymyksenä on, minkälaisia representaatioita yliopiston roolista yhteiskunnassa suomalaiset sanomalehdet välittivät pääkirjoituksissaan uuden yliopistolain säätämistä edeltäneessä uutisoinnissaan? Tutkielmassa eritellään pääkirjoituksista löytyviä yliopiston yhteiskunnallista roolia koskevia merkitysjärjestelmiä eli diskursseja käyttäen menetelmänä Teun van Dijkin diskurssianalyysia. Yliopiston roolia koskevia representaatioita tarkastellaan Jürgen Habermasin tiedon intressien teoriaan peilaten. Muita keskeisiä teoreetikkoja ovat Gerard Delanty, Henry Etzkowitz, Helga Nowotny, Jean-Francois Lyotard, Andy Green ja Marek Kwiek. Yliopiston kolmannen tehtävän korostumista pohjustetaan historiallisella kuvauksella modernin yliopiston synnystä ja yliopistoinstituution kehityksestä Euroopassa ja tarkemmin Suomessa. Työssä käydään myös läpi tutkimusta, joka pureutuu kansallisvaltion ja yliopistoinstituution historiallisen siteen purkautumiseen ja yliopiston toiminnan legitimiteetin uudelleenmäärittelyyn. Lisäksi nostetaan esiin näkemyksiä tiedon tuotannon monopolin irtautumisesta yliopistolta yhä suuremmalle joukolle toimijoita. Analyysia taustoitetaan myös uuden yliopistolain ja sen taustalla olleen ylikansallisen koulutuspolitiikan konsensuksen kautta. Pääkirjoituksissa esiintyneitä yliopiston yhteiskunnallisen roolin saamia merkityksiä tarkastellaan ensin lehtikohtaisesti, minkä jälkeen pääkirjoitusten sisältämistä representaatioista muodostetaan diskursseja. Aineistosta muodostui viisi diskurssia: globaalin selviämistaistelun diskurssi, lokaalin identiteetin diskurssi, maineenrakennuksen diskurssi, panos-tuotos-diskurssi ja myyttisen humboldtilaisuuden diskurssi. Yliopisto representoitiin alueellisen identiteetinrakennuksen ja integraation välineenä ja sellaiseksi alueen integraation välineeksi, jolle valtio on prosessin laidalla oleva tukiverkko. Alueen integraation välineeksi representoitu yliopisto esitettiin samalla globaalille huipulle tähtäämisen myötä legitimoituvaksi instituutioksi. Yliopisto representoitiin siis glokaalin huipulle nousun välineenä. Pääkirjoituksissa epäpolitisoitiin yliopiston ja alueen välinen yhteys sekä yliopiston ja elinkeinoelämän välinen yhteys. Globaalin selviämistaistelun ja myyttisen humboldtilaisuuden välinen merkityskamppailu kulki läpi aineiston. Yliopisto representoitiin teknisen tiedon intressin mukaisesti välineeksi globaalin kilpailukyvyn nostamiseksi. Toisaalta yliopisto esitettiin myös myyttisen humboldtilaiseksi puhdasta tutkimusta tekeväksi ympäröivästä yhteiskunnasta eristäytyneeksi instituutioksi. Aineistossa ei representoitu yliopistoa emansipatorista tiedon intressiä toteuttavana instituutiona vaihtoehtona teknisen tiedon intressin mukaisille representaatioille. Myöskään kommunikatiivisen tiedon intressin mukainen yliopisto ei tullut aineistossa esiin. Aineistossa annettiin vastoin tutkimuskirjallisuuden näkemyksiä yliopistolle legitiimin tiedon monopolin haltijan rooli. Pääkirjoituksissa representoitiin valtiovallan, yksityisen sektorin ja tiedeyhteisön yliopistoa koskevia intressejä. Kansalaisyhteiskunnan ja yliopiston välistä vuorovaikutusta aineisto ei nostanut esiin. Keskeisimmäksi jatkotutkimuksen aiheeksi identifioitiin tämän myötä yliopiston ja kansalaisyhteiskunnan toimijoiden välisen vuorovaikutuksen tarkastelu.

Size dependence of the bulk modulus of semiconductor nanocrystals from first-principles calculations

The variation in the bulk modulus of semiconductor nanoparticles has been studied within first-principles electronic-structure calculations using the local density approximation (LDA) for the exchange correlation. Quantum Monte Carlo calculations carried out for a silicon nanocrystal Si87H76 provided reasonable agreement with the LDA results. An enhancement was observed in the bulk modulus as the size of the nanoparticle was decreased, with modest enhancements being predicted for the largest nanoparticles studied here, a size just accessible in experiments. To access larger sizes, we fit our calculated bulk moduli to the same empirical law for all materials, the asymptote of which is the bulk value of the modulus. This was found to be within 2-10% of the independently calculated value. The origin of the enhancement has been discussed in terms of Cohen's empirical law M.L. Cohen, Phys. Rev. B 32, 7988 (1985)] as well as other possible scenarios.

The top 100 questions of importance to the future of global agriculture

Despite a significant growth in food production over the past half-century, one of the most important challenges facing society today is how to feed an expected population of some nine billion by the middle of the 20th century. To meet the expected demand for food without significant increases in prices, it has been estimated that we need to produce 70-100 per cent more food, in light of the growing impacts of climate change, concerns over energy security, regional dietary shifts and the Millennium Development target of halving world poverty and hunger by 2015. The goal for the agricultural sector is no longer simply to maximize productivity, but to optimize across a far more complex landscape of production, rural development, environmental, social justice and food consumption outcomes. However, there remain significant challenges to developing national and international policies that support the wide emergence of more sustainable forms of land use and efficient agricultural production. The lack of information flow between scientists, practitioners and policy makers is known to exacerbate the difficulties, despite increased emphasis upon evidence-based policy. In this paper, we seek to improve dialogue and understanding between agricultural research and policy by identifying the 100 most important questions for global agriculture. These have been compiled using a horizon-scanning approach with leading experts and representatives of major agricultural organizations worldwide. The aim is to use sound scientific evidence to inform decision making and guide policy makers in the future direction of agricultural research priorities and policy support. If addressed, we anticipate that these questions will have a significant impact on global agricultural practices worldwide, while improving the synergy between agricultural policy, practice and research. This research forms part of the UK Government's Foresight Global Food and Farming Futures project.

Complexity of distance paired-domination problem in graphs

Suppose G = (V, E) is a simple graph and k is a fixed positive integer. A subset D subset of V is a distance k-dominating set of G if for every u is an element of V. there exists a vertex v is an element of D such that d(G)(u, v) <= k, where d(G)(u, v) is the distance between u and v in G. A set D subset of V is a distance k-paired-dominating set of G if D is a distance k-dominating set and the induced subgraph GD] contains a perfect matching. Given a graph G = (V, E) and a fixed integer k > 0, the MIN DISTANCE k-PAIRED-DOM SET problem is to find a minimum cardinality distance k-paired-dominating set of G. In this paper, we show that the decision version of MIN DISTANCE k-PAIRED-DOM SET iS NP-complete for undirected path graphs. This strengthens the complexity of decision version Of MIN DISTANCE k-PAIRED-DOM SET problem in chordal graphs. We show that for a given graph G, unless NP subset of DTIME (n(0)((log) (log) (n)) MIN DISTANCE k-PAIRED-Dom SET problem cannot be approximated within a factor of (1 -epsilon ) In n for any epsilon > 0, where n is the number of vertices in G. We also show that MIN DISTANCE k-PAIRED-DOM SET problem is APX-complete for graphs with degree bounded by 3. On the positive side, we present a linear time algorithm to compute the minimum cardinality of a distance k-paired-dominating set of a strongly chordal graph G if a strong elimination ordering of G is provided. We show that for a given graph G, MIN DISTANCE k-PAIRED-DOM SET problem can be approximated with an approximation factor of 1 + In 2 + k . In(Delta(G)), where Delta(G) denotes the maximum degree of G. (C) 2012 Elsevier B.V All rights reserved.

Effective Mass-Driven Structural Transition in a Mn-Doped ZnS Nanoplatelet

Mn doping in ZnS nanoplatelets has been shown to induce a structural transition from the wurtzite to the zinc blende phase. We trace the origin of this transition to quantum confinement effects, which shift the valence band maximum of the wurtzite and zinc blende polyrnorphs of ZnS at different rates as a function of the nanocrystal size, arising from different effective hole masses in the two structures. This modifies the covalency associated with Mn incorporation and is reflected in the size-dependent binding energy difference for the two structures.

Advances in base- and mobile-station aided cooperative wireless communications : An overview

In recent years, there has been an upsurge of research interest in cooperative wireless communications in both academia and industry. This article presents a simple overview of the pivotal topics in both mobile station (MS)- and base station (BS)- assisted cooperation in the context of cellular radio systems. Owing to the ever-increasing amount of literature in this particular field, this article is by no means exhaustive, but is intended to serve as a roadmap by assembling a representative sample of recent results and to stimulate further research. The emphasis is initially on relay-base cooperation, relying on network coding, followed by the design of cross-layer cooperative protocols conceived for MS cooperation and the concept of coalition network element (CNE)-assisted BS cooperation. Then, a range of complexity and backhaul traffic reduction techniques that have been proposed for BS cooperation are reviewed. A more detailed discussion is provided in the context of MS cooperation concerning the pros and cons of dispensing with high-complexity, power-hungry channel estimation. Finally, generalized design guidelines, conceived for cooperative wireless communications, are presented.

Microscopic description of the evolution of the local structure and an evaluation of the chemical pressure concept in a solid solution

Extended x-ray absorption fine-structure studies have been performed at the Zn K and Cd K edges for a series of solid solutions of wurtzite Zn1-xCdxS samples with x = 0.0, 0.1, 0.25, 0.5, 0.75, and 1.0, where the lattice parameter as a function of x evolves according to the well-known Vegard's law. In conjunction with extensive, large-scale first-principles electronic structure calculations with full geometry optimizations, these results establish that the percentage variation in the nearest-neighbor bond distances are lower by nearly an order of magnitude compared to what would be expected on the basis of lattice parameter variation, seriously undermining the chemical pressure concept. With experimental results that allow us to probe up to the third coordination shell distances, we provide a direct description of how the local structure, apparently inconsistent with the global structure, evolves very rapidly with interatomic distances to become consistent with it. We show that the basic features of this structural evolution with the composition can be visualized with nearly invariant Zn-S-4 and Cd-S-4 tetrahedral units retaining their structural integrity, while the tilts between these tetrahedral building blocks change with composition to conform to the changing lattice parameters according to the Vegard's law within a relatively short length scale. These results underline the limits of applicability of the chemical pressure concept that has been a favored tool of experimentalists to control physical properties of a large variety of condensed matter systems.

Levels of Alpha-Toxin Correlate with Distinct Phenotypic Response Profiles of Blood Mononuclear Cells and with agr Background of Community-Associated Staphylococcus aureus Isolates

Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of alpha-toxin than did the proliferative supernatants. Addition of alpha-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, delta-toxin or phenol soluble modulin alpha-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

Key challenges for the creation and maintenance of specialist protein resources

As the volume of data relating to proteins increases, researchers rely more and more on the analysis of published data, thus increasing the importance of good access to these data that vary from the supplemental material of individual articles, all the way to major reference databases with professional staff and long-term funding. Specialist protein resources fill an important middle ground, providing interactive web interfaces to their databases for a focused topic or family of proteins, using specialized approaches that are not feasible in the major reference databases. Many are labors of love, run by a single lab with little or no dedicated funding and there are many challenges to building and maintaining them. This perspective arose from a meeting of several specialist protein resources and major reference databases held at the Wellcome Trust Genome Campus (Cambridge, UK) on August 11 and 12, 2014. During this meeting some common key challenges involved in creating and maintaining such resources were discussed, along with various approaches to address them. In laying out these challenges, we aim to inform users about how these issues impact our resources and illustrate ways in which our working together could enhance their accuracy, currency, and overall value. Proteins 2015; 83:1005-1013. (c) 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat

During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.