Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes

Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70 % amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future

Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Losing cabin pressure - A study on the forces behind the proposal to derogate intercontinental flights from Directive 2003/87/EC

In 2008, with support from all institutions, the EU decided to include aviation into its Emissions Trading System (ETS) in order to mitigate greenhouse emissions from the sector. Initially, this decision received criticism, both internally and internationally, demonstrating the controversies surrounding it. Subsequently, in November 2012 the Commission presented a proposal to temporarily derogate intercontinental flights from the original decision. While the official explanation was that it wished to facilitate a global solution at the International Civil Aviation Organisation (ICAO), the specific circumstances around the derogation proposal are unclear. Since aviation is a global industry, multiple actors and interest constellations, both internally and internationally, have participated. A key factor in this discussion, and overall within environmental policy, is therefore the influence and impact by specific actors within the policy process. This master thesis examines why the proposal was presented, by looking closer at what actors that have been present and essential during the process leading up to the derogation proposal. A qualitative method was applied where a theoretical approach, including principles of influence, power and setting the agenda, has been established to answer how the proposal was made possible. In order to further explain the process, new institutionalism has provided additional perspectives, to explain why the proposal was presented. The study has found that both internal and external pressure led the EU to present the derogation proposal

Utvärdering av lösningar för virtuell cockpit inom flygsimulering

Virtual Reality has become widespread in areas other than gaming. How this type of technology can be used in, for example, flight simulation still needs to be discovered. In this thesis virtual reality technology and free-hand interactions are examined in the context of a fighter jet cockpit. Design principles and visualization techniques are used to examine how a virtual reality cockpit and interactions can be designed with high usability. From user test sessions, and accompanying questionnaire, some guidelines for how this type of interaction should be designed are gathered. Specifically, how objects that can be interacted with, and the distance to them should be visualized, with regards to free-hand interaction. Also, different ways of providing feedback to the user are discussed. Finally, it is determined that the technology used is a good fit for the context and task, but the implementation of interaction components needs more work. Alternative ways of tracking hand motions and other configurations for the sensors should be examined in the same context

Livet med Aspergers syndrom : En litteraturstudie

Idag lever upp till 48 personer utav 10 000 med drag av Aspergers syndrom. Då kunskaperna ofta är otillräckliga inom ämnesområdet kan detta orsaka en bristfällig förståelse i mötet med vårdpersonalen. Detta medför emellanåt ett lidande för personer med Aspergers syndrom. Syftet med studien var att belysa livsvärlden hos personer med Aspergers syndrom och deras möte med den svenska vården. Metoden som användes var litteraturstudie med kvalitativ ansats. Resultatet visade att personer med Aspergers syndrom upplevde svårigheter i det sociala samspelet med andra människor. Livsvärlden hos personerna gestaltade sig ofta i att de engagerade sig i olika former av specialintressen, vilket berodde på att dessa var bekanta och därmed hade de en ångestlindrande effekt. I längden bidrog detta till en avskärmning från omvärlden och att en redan dåligt fungerande social kommunikation försvårades, vilket även påverkade vårdrelationen. Slutsatsen som kan dras är att personer med Aspergers syndrom inte alltid upplever ett professionellt bemötande av vården

Simulering av en deterministisk kanalmodell för mobil kommunikation

The last decade there has been an enormous expansion in the area of wireless communication. As new services and devices are introduced, and more information is sent between an increasing number of users, more bandwidth is required and the spectrum becomes more limited. To increase capacity in cellular networks, cells can be made smaller and smaller. To be able to plan picocells, such as an indoor environment, in an efficient manner, it is important to have a more detailed understanding about the channel characteristics. Further ways to improve radio communication is to make use of more efficient encoding and receiving techniques, such as spread spectrum. Also when testing new techniques, knowledge about the channel characteristics and limitations are of interest. This thesis models the channel characteristics of an indoor deterministic environment with a simulator using ray tracing techniques. To make the environment as realistic as possible, the physical properties of construction materials are taken into account. The simulator is able to track each individual radio wave, making it possible to calculate interesting parameters such as received power, phase, and direction-of-arrival. The simulator operates in 2D-environments. A lot of work have been done to extend the simulator to a 3D-version, although some problems still remains to be solved

Livet med Aspergers syndrom : En litteraturstudie

Idag lever upp till 48 personer utav 10 000 med drag av Aspergers syndrom. Då kunskaperna ofta är otillräckliga inom ämnesområdet kan detta orsaka en bristfällig förståelse i mötet med vårdpersonalen. Detta medför emellanåt ett lidande för personer med Aspergers syndrom. Syftet med studien var att belysa livsvärlden hos personer med Aspergers syndrom och deras möte med den svenska vården. Metoden som användes var litteraturstudie med kvalitativ ansats. Resultatet visade att personer med Aspergers syndrom upplevde svårigheter i det sociala samspelet med andra människor. Livsvärlden hos personerna gestaltade sig ofta i att de engagerade sig i olika former av specialintressen, vilket berodde på att dessa var bekanta och därmed hade de en ångestlindrande effekt. I längden bidrog detta till en avskärmning från omvärlden och att en redan dåligt fungerande social kommunikation försvårades, vilket även påverkade vårdrelationen. Slutsatsen som kan dras är att personer med Aspergers syndrom inte alltid upplever ett professionellt bemötande av vården

Förändras axelrörligheten hos unga handbollsspelare efter 6 veckors rörlighetsträning?

Sammanfattning Bakgrund: Axelsmärta är vanligt förekommande inom handboll med en rapporterad punktprevalens mellan 19-36% innan säsongsstart och medelprevalens under en träningsvecka när det är säsong på 28%. Olika riskfaktorer har diskuterats där inskränkt rörlighet i axelleden är en av dem. Ett handbollskast kan uppmäta 130km/h med en boll som väger nästan ett halvt kilo och detta ställer stora krav på axelleden. Minskad rörlighet (främst inåtrotation) med en ökad utåtrotation till följd av posterior-inferior kontraktur av ledkapseln i axeln är en förändring som har kunnat påvisas vid tidigare studier hos kastidrottare. Syfte: Studiens syfte var att undersöka om axelrörligheten förändrades efter sex veckors rörlighetsträning där deltagarna skulle utföra 3 övningar 2 gånger i veckan under dessa sex veckor hos en grupp unga handbollsspelare. Ett ytterligare syfte var att undersöka hur många av deltagarna som påvisade GIRD-fenomenet före och efter interventionen. Studiedesign: En interventionsstudie med för- och eftermätningar av inåt- och utåtrotationen i axelleden. Metod: Studien inkluderade 16 handbollsspelande gymnasieelever. Mätningar av inåt- och utåtrotation i axelleden utfördes med sex veckors mellanrum för att undersöka om det skett en förändring av rörligheten. Under dessa sex veckor skulle tre rörlighetsövningar utföras av studiedeltagarna 2 gånger per vecka. För att undersöka om det skedde en signifikant förändring utfördes ett parat t-test. Ingen kontrollgrupp var med i studien. Etik: Projektplan skickades in till vårdvetenskapliga etiknämnden på Lunds universitet och de hade inga invändningar på genomförandet av studien. All data behandlades konfidentiellt. Resultat: Efter sex veckors intervention ökade inåtrotationen i kastarmen hos deltagarna med 6,8 grader (95% CI:4,0-9,6) p=0,0001. Inåtrotationen i den ickedominanta armen ökade med 7,8 grader (95% CI:4,6-10,8) p=0,0001. Vid första mättillfället var det fyra deltagare som påvisade GIRD. Denna siffra hade reducerats till två deltagare vid det andra mättillfället efter genomförd intervention. Ingen av deltagarna hade mindre än 90 graders utåtrotation vid något av mättillfällena. Konklusion: I den undersökta gruppen skedde en signifikant ökning av inåtrotationen i både kastarmen och den ickedominanta armen efter 6 veckors intervention med rörlighetsträningsprogram