Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background: Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim: To identify genetic variants associated with forearm BMD and forearm fractures. Methods: BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results: We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (

β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed

Purpose: In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca2+) handling. Accumulation of hydrogen cation (H+) has been shown to impact Ca2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca2+ and H+ coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions. Methods: Twenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day−1 of BA (n=12) or placebo (PLA; n=11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions. Results: BA supplementation had no effect on voluntary or electrically  evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions  during both resting (3±13%; 19±26%) and potentiated (1±15%; 2±20%) twitch contractions. Conclusions: The mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue. Trial registration The trial is registered with Clinicaltrials.gov, ID number NCT02819505

Käyttöliittymäkonseptin käyttäjätutkimus : tapaus F-secure Freedome-VPN-sovellus

Tämän opinnäytetyön tarkoituksena on selvittää, miten tuotteen konseptivaiheessa olevaa käyttöliittymää kannattaisi tutkia käyttäjätutkimuksen menetelmin. Tavoitteena on selvittää taustoja käyttäjätutkimuksen tarkoituksesta; millaisia vaihtoehtoja tutkimusmetodeissa on, miten hyvin valittu metodi soveltuu käyttöliittymäkonseptin tutkimiseen ja millaisia löydöksiä valitulla tutkimusmetodilla saadaan. Opinnäytetyössä käytetään hyväksi tapausesimerkkiä suomalaiselle tietoturvayhtiölle F-Securelle fokusryhmähaastattelun menetelmin toteutettua Freedome-VPN-sovelluksen varhaisen käyttöliittymäkonseptin käyttäjätutkimusta. Opinnäytetyön teoriaosuus alkaa perehtymällä käyttäjän rooliin tuotekehityksessä. Luvussa käydään myös läpi taustoja käyttäjätiedon takana. Tämän jälkeen siirrytään teoriaan käyttäjätiedon keräämisen takana. Kyseisessä luvussa pohditaan käyttäjätiedon keräämisen metodeita sekä valitaan yksi malli tutkimusmetodin valintaan. Mallin pohjalta valitaan tapausesimerkissä käytetty käyttäjätutkimuksen metodi, fokusryhmähaastattelu, joka esitellään yksityiskohtaisemmin. Työn käytännön osuudessa käydään läpi F-Securen Freedome-VPN-Sovelluksen käyttäjätutkimus. Kappaleessa esitellään fokusryhmähaastattelun toteutus käytännössä, jonka jälkeen perehdytään tapausesimerkin käyttäjätutkimuksessa löydettyihin yksityiskohtaisiin tuloksiin. Tapausesimerkissä suoritetun fokusryhmähaastattelun pohjalta voidaan todeta, että fokusryhmähaastattelu oli toimiva metodi kyseisen käyttöliittymäkonseptin tutkimisessa. Osallistujilta saatiin kattavaa tietoa sekä ajatuksista konseptia kohtaan. Vaikka fokusryhmähaastattelu ei ole perinteinen menetelmä käytettävyysongelmien etsimiseen tuotteen käytön puutteen johdosta, tehtiin haastattelussa myös tärkeitä käytettävyyteen liittyviä löydöksiä.The main theme of this thesis is to find out how to conduct a user study on a user interface concept by using user-experience research methods. The goal is to clarify the purpose of user study; What kind of user-experience methods are available, how well does the selected method apply to the study of a user interface concept and what kind of results does it generate. The thesis utilizes a case study done for the Finnish security company F-Secure. The case study examined the early version of a user interface concept for F-Secure Freedome VPN application’s PC version. The theoretical background of the thesis begins by studying the user’s role in product development. Then the thesis proceeds to the theory of collecting user data. This chapter also examines the methods of collecting the user data as well as introduces one model to select the right user-experience research method. By using this model, a focus group is selected to a closer examination and also to be used as a research method later on in the case example of the thesis. The practical part of the thesis is an overview to the F-Secure Freedome VPN application’s user research. This chapter describes how to perform a focus group interview in practice, after which the thesis focuses on the detailed findings of the case example’s user study. The case study indicated that a focus group is a valid method when studying user interface concepts. Participants gave comprehensive information and ideas about the concept and even though focus group interview is not a traditional method for finding usability problems due to lack of use of the product, some important usability findings was done in the user study

Chromatic Function Analysis. An instrument for function analysis, improvisation and composition

The purpose of this investigation was to create a chromatic function analysis which can help to guide and give other viewpoints to harmonic relations and to be an instrument for supporting me in my artistic process of improvisation and composition. The new model is based mostly on Riemann analysis but I have in addition incorporated different theorists, Söderholm, Ingelf, Levy and Jersild, adaptations of Riemann analysis. The new model is evaluated using different classical pieces. It is as well applied to two poems by Edith Södergran and one fuge, all composed by me. Looking at my compositions the experience was that I felt more confident in my way of making music. With this confidence I dared to go further with my music and to express myself more. The chromatic function analysis instrument supports and enforces my artistic process in the arts of composition

Chromatic Function Analysis- An instrument for improvisation

The purpose of this investigation is to become a better improviser at the organ. I will use, The Chromatic Function Analysis Model, abbreviated as TCFAM, as a method to deconstruct material and later reconstruct material, on which I will make improvisations. I want to see how well TCFAM can support improvisation and, in the process, become a better improviser. The method is applied to describe harmonic relations in music, music that is built on harmony. By using this method, that works with describing harmony, it’s possible to make statistics. The statistics will show how common certain chord progressions are, how often chords are applied and what relations chords have to each other. A limitation is that this method is only intended to address harmony. The method will be applied on various organ music, organ repertoire, that is strongly linked to improvisation and transcribed improvisations. The repertoire is chosen from different epochs and to cover different usage of harmony from different time eras. This will show how well the method applies to different genres depending on the certain time era. Apart from existing repertoire, the method will also be applied on transcribed improvisations to explore how various organists work with improvisation. To me, improvisation could be thought of as live composition, like a game of chess in which sometimes a progression of moves is custom but depending on what game you play; you must change your move within the structure. The method allows me to create the many structures, that will be applied for improvisation. TCFAM will be one possible way to approach improvisation and I will investigate if the method can support me in improving my artistic improvisation skills by addressing following questions: 1. Will the data collected and processed through TCFAM support my creativity in the process of improvising? 2. By using this method what do I learn? 3. Can TCFAM be an instrument for analysis of transcribed improvisations or compositions to work as a generating principle/tool for improvisation? In this thesis TCFAM will be used to study what harmonies improvisers and composers use and from the collected data construct blueprints, allowing me to approach improvisation. By using this method, I made fourteen improvisations in different styles, which demonstrate how the method can work as a tool to approach improvisation. The intent is not to copy someone else but to be able to deconstruct a style of music and be able to generate a musical language that I can use in my own artistic practice. I learned that this method can work as a method to support improvisation. Other affordances that this method can give is its possibility to find patterns. By patterns I mean a harmonic sequence of any sort that is repeated somehow throughout the piece. An analogy would be the jazz pianist improvising at the piano. He uses the same chords as an underlying structure but by using scales, motives and other concepts the improviser hides the harmonic structure, so even though much is going on, the framework being the harmony, is the same. Another affordance is the method’s possibility of collecting data on harmony. The data could be applied to verify music which author is unknown to known material, showing the content’s probability of being by the same author. In this case the method could be applied as a tool to show probability

Design of modular dropout system

Denna rapport syftar till att ta fram ett modulärt dropout-system till en cykel, ett system som kopplar bakhjulet till ramen (det saknas en bra svensk översättning). Ett modulärt dropout-system gör det möjligt för en cykelram att använda flera olika typer av dropouts, vilket betyder att cykelramen kan anpassas efter olika användningsområden. Systemet består av ett fäste för dropoutsen och själva dropoutmodulerna. Det finns flera typer av modulära dropouts system idag men ingen standardisering av dem. Vid framtagning av systemet används generativ design i form av topologioptimering och en utvärdering av dess effekt på cykeldesign görs. System modellerades i CAD-programmet Solid Edge och innefattar ett fäste och tre typer av moduler, vilka utgår ifrån uppdragsgivarens krav. Systemet ska vara kompatibelt med bakhjul som har 120 mm och 135 mm breda nav där axeldiametern är 9 mm, samt 142 mm breda nav med en 12 mm axeldiameter, vilka motsvarar de tre olika modulerna. Designen var till en början enkel och främst fokuserad på de olika navens kompabilitet samt modulernas infästning. Anledningen till det var att Solid Edges inbyggda generative design-funktion valdes att användas. Denna funktion optimerar designen topologiskt utifrån användarens givna geometriska begränsningar samt de laster som designen utsätts för. Detta genererar en design av komplex geometri och används därför som en mall för hur den grova designen ska förbättras. Den förbättrade designens hållfasthetsegenskaper verifierades med FEM analyser som genomfördes med Discovery, vilket är inbyggd i CAD-programmet. Beräkningar på skruvförbandet mellan dropoutmodulerna och deras fäste utfördes, samt svetsförbandet mellan cykelramen och systemet, för att säker ställa att inga oönskade effekter på cykelns prestanda eller säkerhet uppkommer. Det resulterande systemet bedöms uppfylla kraven och ha tillräckliga hållfasthetsegenskaper, men det bedöms inte vara ett optimalt system. Det finns osäkerheter i det lastfall som användes för analyser av systemet och har därför dimensionerats mot en säkerhetsfaktor som tagits fram enligt Pugsley safety factor approach. Dessutom görs ett antal antagande vid beräkning av skruvförbandet. Det finns många fördelar med att använda Generative Design för att designa cyklar, men data på de laster som cykeln utsätts för och additiv tillverkning måste utvecklas mer för att nå sin fulla potential.This report aims to develop a modular dropout system for a bicycle. A modular dropout system allows a bike frame to use various types of dropouts, enabling customization for different usage scenarios. The system consists of a dropout mount and the dropout modules themselves. While there are several types of modular dropout systems available today, there is no standardization for them. In the development of the system, generative design is used in the form of topology optimization, and an evaluation of its effect on bicycle design is conducted. The system was modelled in the CAD program Solid Edge and includes a mount and three types of modules based on the client's requirements. The system is designed to be compatible with rear wheels with 120mm and 135mm wide hubs with a 9mm axle diameter, as well as 142mm wide hubs with a 12mm axle diameter, corresponding to the three different modules. Initially, the design was focused on the compatibility of the different hubs and the attachment of the modules, before utilizing Solid Edge's built-in generative design function. This function optimizes the design topologically based on user-defined geometric constraints and the loads the design will experience, resulting in a complex geometry design, which was used as a template for improving the initial design. The improved design's strength properties were verified using FEM analysis conducted with Discovery, an embedded function in the CAD program. Calculations were performed on the screw connections between the dropout modules and their mounts, as well as the welds between the bike frame and the system, to ensure that there were no adverse effects on the bike's performance or safety. The resulting system is deemed to meet the requirements and has adequate strength properties, but it is not considered an optimal system. There are uncertainties in the load cases used for analysing the system, and it has, therefore, been dimensioned with a safety factor according to Pugsley safety factor approach. Additionally, several assumptions were made when calculating the screw connections, making the results unclear. There are many advantages to using GD to design bicycles, but data on the forces acting on the bike as well as additive manufacturing needs to be further developed to reach its full potential

Competition at public procurement : Particularly regarding rogue tenders

Lagarna om offentlig upphandling har som syfte att bidra till att den inre marknaden inom EU upprätthålls. Osund konkurrens förhindrar att offentliga myndigheter gör bra affärer. Förekomsten av oseriösa anbudsgivare och bristande kontroller från upphandlande myndigheter gör att skattepengar som skulle kunna användas inom välfärden går förlorade. Upphandlingsreglerna ska säkerställa att myndighet inte använder offentliga medel på ett otillbörligt sätt och därav säkra att inga leverantörer gynnas eller missgynnas. Upphandlingsreglerna har en lång historisk utveckling och ämnar konstant att bli modernare och enklare samt garantera en rättvis konkurrens mellan leverantörerna. Oseriösa anbud kan förekomma i flera olika former. I uppsatsen redogörs för vilka dessa former kan vara, samt hur upphandlande myndighet har möjlighet att med hjälp av upphandlingsreglerna förhindra att sådana anbud antas. Angående förhindrandet av oseriösa anbud leder till att bevisfrågan blir av intresse. Bevisbördans placering gällande ett anbuds seriositet redogörs för med hjälp av främst HFD:s nya domar om onormalt låga anbud men även EU-domstolens praxis. Det spekuleras även över hur den eventuella förseningen av införlivandet av det nya upphandlingsdirektivet kommer att påverka de offentliga upphandlingarna i Sverige. I analysen utreds frågeställningarna är det möjligt att förhindra att oseriösa anbud antas och hur påverkar oseriösa anbud konkurrensen vid offentlig upphandling där bland annat slutsatsen blir att upphandlande myndigheters kontroll av leverantörer bör vidgas samt att det är av vikt att uppnå en sund marknad med bra konkurrens, vilket innebär att oseriösa anbud måste motarbetas. I dagsläget får det fortfarande anses oklart gällande begreppen oseriösa anbud samt oseriösa leverantörer, men insikten om att en motarbetning är behövlig för att uppnå EU:s inre marknad, får anses vara upp-märksammad.