Venous thromboembolism: Risk factors, comorbidities, and treatment-associated risk of bleedings

Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease, consisting mainly of deep vein thrombosis (DVT) and pulmonary embolism (PE). Since VTE often is a preventable disease, knowledge of risk factors is critical. Following a VTE, many patients are subjected to extended anticoagulant treatment. However, the bleeding risk during extended treatment is largely unknown. Aim: To study risk factors in patients with VTE and to determine the occurrence of major bleeding during VTE treatment. Methods: Paper I: 1.6 million men from The Swedish Military Service Conscription Register were grouped based on BMI and followed through nationwide registries to determine the risk of a first-time VTE. Papers II-IV: The National Patient Register, the National Cause of Death Register, the National Prescribed Drug Register, and the Total Population Register were used to identify almost 300,000 patients with first-time PE or DVT and 1,200,000 matched controls. PE and DVT patients and their respective controls were compared regarding comorbidities and temporary provoking factors (II), the prevalence of different cancers (III), and, between 2014– 2020, the risk of bleeding during anticoagulant treatment (IV). Results: Paper I: Men who were overweight or obese at enlistment had a high risk of VTE later in life. Paper II: Patients with PE more often had underlying cardiovascular disease, while patients with DVT were more likely to have recent musculoskeletal surgery or fracture. Paper III: VTE had a strong association with pancreatic, brain, or liver cancer, while the association was weak with recent diagnoses of bladder/urinary tract cancer, kidney cancer, or uterine cancer. Paper IV: During initial treatment (0–6 months), patients treated with apixaban had a lower bleeding risk than patients treated with warfarin or rivaroxaban. During extended treatment (6 months–5 years), both apixaban and rivaroxaban had a low bleeding risk, lower than warfarin. Conclusion: The increasing prevalence of obesity might imply an increase in VTE in the coming decades. Patients with cardiopulmonary disease had a higher risk of PE than DVT. Risks of VTE differ widely for various cancers. Apixaban carried a lower risk of bleeding than rivaroxaban and warfarin in the initial treatment, while both apixaban and rivaroxaban had a low risk of bleeding, and lower than warfarin, in extended treatment. These findings are important for VTE prophylaxis and treatment in clinical praxis

Ectopic A-lattice seams destabilize microtubules

Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe

Beskattning av idrottsutövare - intern internationell personbeskattning ur ett elitidrottsperspektiv

Idrottsmarknaden har gått igenom stora förändringar de senaste årtiondena, vilket har lett till en på många sätt ökad internationell konkurrens. Från en tid när även många av de stora stjärnorna sågs som glada amatörer har professionalismen inom idrotten ökat och allt fler utövare försörjer sig på sitt idrottande. På lagidrottsområdet spelar ländernas interna regler stor roll för klubbarnas konkurrenskraft då de påverkar möjligheten att erbjuda löner och villkor som kan locka de stora stjärnorna. Med hänsyn till att harmoniseringen på skatteområdet är högst begränsad inom EU kan de regionala skillnaderna i skattesystemen variera avsevärt, varför det finns anledning att se närmare på hur dessa samspelar med idrotten. Utövare inom de individuella idrotterna har större möjlighet att själva välja sin bosättning än vad lagidrottarna har, eftersom de förstnämndas idrottande inte på samma sätt är bundet till en viss plats eller land. För dessa utövare är praktiska skäl ofta huvudorsaken vid val av bosättning, men även ett lands skatteregler är något som många gånger tas hänsyn till. Skattereglerna är inte minst avgörande i de fall idrottsstjärnor väljer att flytta ut från Sverige efter att karriären har avslutats. Den här uppsatsen undersöker, med det svenska interna regelverket som utgångspunkt, skatterättens förhållande till elitidrottsutövare. Utöver att beskriva det teoretiska ramverket syftar uppsatsen också till att tydliggöra och behandla de praktiska skatterättsliga frågor som elitidrottsutövare i Sverige har att brottas med

Konstskapande med kroppen som biografi. Att navigera mellan det okända och det välkända

Fia Adler Sandblad (MA, MFA) is an actor and playwright who 1992 founded ADAS musikaliska teater in Gothenburg, where she continues to be active. She has worked extensively with projects concerning the staging of biographical experiences.In this article I seek to describe how to use performativity and acting skills in order to get in touch with and articulate once owns life-experiences beyond the explicit and well known. The question is how I, by physical and vocal practice, can approach fragments of my silent past and capture some of its emotional and existential meanings in order to share it with an audience. I highlight the necessity to articulate these silent experiences and make them part of a public discourse. I reason about my autobiographical position, what parts of reality I choose for the story and what fiction has to do with it

Mammalian end binding proteins control persistent microtubule growth

© 2009 Komarova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0. The definitive version was published in Journal of Cell Biology 184 (2009): 691-706, doi:10.1083/jcb.200807179.End binding proteins (EBs) are highly conserved core components of microtubule plus-end tracking protein networks. Here we investigated the roles of the three mammalian EBs in controlling microtubule dynamics and analyzed the domains involved. Protein depletion and rescue experiments showed that EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes. Furthermore, we demonstrated in vitro and in cells that the EB plus-end tracking behavior depends on the calponin homology domain but does not require dimer formation. In contrast, dimerization is necessary for the EB anti-catastrophe activity in cells; this explains why the EB1 dimerization domain, which disrupts native EB dimers, exhibits a dominant-negative effect. When microtubule dynamics is reconstituted with purified tubulin, EBs promote rather than inhibit catastrophes, suggesting that in cells EBs prevent catastrophes by counteracting other microtubule regulators. This probably occurs through their action on microtubule ends, because catastrophe suppression does not require the EB domains needed for binding to known EB partners.This work was supported by the Netherlands Organization for Scientifi c Research grants to A.A., by Funda ç ã o para a Ci ê ncia e a Tecnologia fellowship to S.M. Gouveia, by a FEBS fellowship to R.M. Buey, by the National Institutes of Health grant GM25062 to G.G. Borisy and by the Swiss National Science Foundation through grant 3100A0-109423 and by the National Center of Competence in Research Structural Biology program to M.O. Steinmetz

Tubulin Dimers Oligomerize before Their Incorporation into Microtubules

In the presence of GTP, purified dimers of α- and β-tubulin will interact longitudinally and laterally to self-assemble into microtubules (MTs). This property provides a powerful in vitro experimental system to describe MT dynamic behavior at the micrometer scale and to study effects and functioning of a large variety of microtubule associated proteins (MAPs). Despite the plethora of such data produced, the molecular mechanisms of MT assembly remain disputed. Electron microscopy (EM) studies suggested that tubulin dimers interact longitudinally to form short oligomers which form a tube by lateral interaction and which contribute to MT elongation. This idea is however challenged: Based on estimated association constants it was proposed that single dimers represent the major fraction of free tubulin. This view was recently supported by measurements suggesting that MTs elongate by addition of single tubulin dimers. To solve this discrepancy, we performed a direct measurement of the longitudinal interaction energy for tubulin dimers. We quantified the size distribution of tubulin oligomers using EM and fluorescence correlation spectroscopy (FCS). From the distribution we derived the longitudinal interaction energy in the presence of GDP and the non-hydrolysable GTP analog GMPCPP. Our data suggest that MT elongation and nucleation involves interactions of short tubulin oligomers rather than dimers. Our approach provides a solid experimental framework to better understand the role of MAPs in MT nucleation and growth

Students envisioning the future.

How can students be included as critical stakeholders in the systems and services provided by a university? To address the whole student experience, we engaged students and employees at a large Swedish university in a vision seminar process to elicit how these groups envisioned an ideal future university, and the necessary changes to technology and organisational structures required to achieve this ideal version. The process entailed six four-hour workshops with four groups consisting of six participants each. A survey instrument was used to follow up on the participants' experiences of participating in the vision seminar process and their thoughts on the future of the university. The results show that the participating students were more positive compared to the university employees. The students envisioned harmonized interdepartmental systems, seamlessly integrating a variety of services into one university-provided solution. The employees envisioned their future work as flexible, enabled by technology providing excellent support without hindering pedagogical and organisational development. Using technological frames, these visions of the future are identified, analysed and discussed in relation to the quality of university education and a holistic view on students' university experience. Finally we discuss the broader implications of the visions on the future of university education

Operative tests of a new system for train traffic control

Tomorrow's train traffic systems requires new strategies and solutions for efficient train traffic control and utilization of track capacity, especially in traffic systems with a high degree of deregulated and mixed traffic. There are many different goals associated with the traffic control tasks and the work of the traffic controllers (dispatchers). Examples are safety, efficiency of the traffic with regard to timeliness and energy consumption, good service and information to passengers and customers etc. Today's traffic control systems and user interfaces do not efficiently support such goals. In earlier research we have analyzed important aspects of the traffic controller's tasks, strategies, decision making, use of information and support systems etc. Based on this research we, together with Banverket (Swedish Rail Administration), have designed prototype systems and interfaces that better can meet future goals and contribute to more optimal use of infrastructure capacity