Toimenpiteiden alueellinen vaihtelu korva-, nenä- ja kurkkutautien erikoisalalla

Lähtö­kohdat Useilla eri­koi­sa­loilla se­kä sai­rauksien lääkkeel­linen hoi­to et­tä toimen­pi­teiden taa­juudet vaihte­levat tervey­den­huollon yksi­köissä. Tä­mä ei välttä­mättä ku­vaa sai­rauksien epä­ta­saista jakau­tu­mista, vaan epäyh­te­näisiä ­hoi­to­pe­rus­teita. Täs­sä tutki­muk­sessa selvi­tettiin kor­va-, ne­nä- ja kurkku­tautien eri­koi­salan taval­listen toimen­pi­teiden mää­rien muu­toksia 2000-lu­vulla ja ver­tailtiin sairaan­hoi­to­piirien suorit­teita väes­töön suhteu­tet­tuna. Sa­malla ar­vioitiin Ter­veyden ja hyvin­voinnin lai­toksen hoitoil­moi­tus­re­kis­terin (Hilmo) luotet­ta­vuutta toimen­pi­de­jak­sojen kuvaa­jana. Mene­telmät Hilmo-re­kis­te­ristä ke­rättiin sairaan­hoi­to­pii­reittäin ai­kuisia kos­kevat tie­dot nielu­ri­sojen pois­ton, ne­nän väli­seinän oi­kaisun ja ne­nän sivuon­te­loiden tähys­tys­leik­kauksen suori­te­mää­ristä vuo­silta 2002–12. Näi­tä luku­määriä ­ver­rattiin sairaa­loiden anes­tesia- ja leikkaus­toi­minnan vertai­sar­vioin­ti­tie­to­kannan (BM-OR) se­kä Hel­singin ja Uu­denmaan sairaan­hoi­to­piirin (HUS) leikkaus­salien toimin­na­noh­jaus­jär­jes­telmän (OPERA) tie­toihin. Tu­lokset Ai­kuisten nielu­ri­sa­leik­kaukset ovat vähen­tyneet 2000-lu­vulla va­jaat 20 % ja ne­nän väli­seinän oikai­su­leik­kaukset run­saat 30 %. Sivuon­te­loiden tähys­tys­ki­rurgian koko­nais­määrä on säi­lynyt en­nallaan. Leikkaus­hoidon toden­nä­köisyys vaih­teli sairaan­hoi­to­pii­reittäin. Konser­va­tii­vi­simman ja aktii­vi­simman sairaan­hoi­to­piirin vä­linen ero oli aikuis­po­tilaan nielu­ri­sa­leik­kauk­sessa yli kaksin­ker­tainen, sivuon­te­loiden tähys­tys­ki­rur­giassa nelin­ker­tainen ja ne­nän väli­seinän oikai­su­leik­kauk­sessa yli kymmen­ker­tainen. Hil­mo- ja BM-OR-tie­to­kan­tojen vä­linen korre­laatio vuo­sina 2010–12 oli erittäin hy­vä. Pää­telmät Aikui­sille suori­tetut ne­nän väli­seinän oi­kaisu, nielu­ri­sa­leikkaus ja sivuon­te­loiden tähys­tys­ki­rurgia edus­tavat toimen­pi­teitä, joi­ta teh­dään kai­kissa eri­kois­sai­raan­hoidon yksi­köissä. Kun­kin toimen­piteen yleisyys vaih­teli sairaan­hoi­to­pii­ristä toi­seen ja väes­töön suhteu­tettu ero saat­toi ol­la monin­ker­tainen. Toden­nä­köi­sesti hoi­toon oh­jaus, mieli­piteet ja re­surssit määrit­te­levät leikkau­sai­heita ole­tettua enemmän.Peer reviewe

Asennussolukonseptin suunnittelu Sustainable Technology Hubiin

Kohdeyritys on rakentanut uuden Sustainable Technology Hubin, jossa tutkimus, tuotekehitys, elinkaaripalvelut ja valmistus toimivat samoissa tiloissa. Yrityksen päätuotteita ovat suuret 4-tahtimoottorit meriteollisuuteen ja voimalaitoksiin. Moottoreiden kokoonpanotyö tehdään asennussoluissa, jotka koostuvat solukohtaisista nostureista, korkeussäädettävistä asennustasoista sekä materiaalinsyöttöpisteistä. Vanhoissa toimitiloissa käytössä olevat asennussolut eivät ole riittävän joustavia sekä niiden asennustasojen turvallisuudessa on puutteita ja uusiin toimitiloihin siirryttäessä nämä ongelmat tulee ratkaista. Tässä työssä tutkimusmenetelmänä käytetään suunnittelututkimusta. Teoriaosassa käsitellään tuotantojärjestelmien suunnittelua ja ergonomian huomioimista suunnittelussa. Työssä tutkitaan käytössä olevia asennussoluratkaisuja kohdeyrityksessä sekä kilpailijoilla. Tutkimuksessa paneudutaan turvallisuuteen, toiminnallisuuteen ja tilankäyttöön vaikuttaviin ratkaisuihin. Työssä luodaan asennussolukonsepti, jonka pohjalta toteutetaan kolme mitoiltaan poikkeavaa variaatiota asennussoluista. Konseptin tärkeimpiä ominaisuuksia ovat materiaalinsyötön ja nosturirakenteiden yhdistäminen tilaa säästävällä rakenteella sekä laajasti säädettävät henkilönostimiksi tyypitettävät asennustasot. Työtason jatke ja kaideratkaisu mahdollistaa geneerisen tuotteen reunojen peittämisen EN ISO14122 vaatimusten mukaisesti. Kehitetty työtason jatke ja kaideratkaisu on saanut paljon positiivista palautetta yrityksen sisällä ja se on todettu toimivaksi, joten sen käyttöä suunnitellaan myös muihin kohteisiin. Kokonaisuuden jakaminen rajapintoihin ja modulaarisen rakenteen käyttäminen alensi suunnittelukustannuksia 50 % sekä mahdollisti toteutuksen jakamisen eri toimijoille.The target company has built a new Sustainable Technology Hub, where research, product development, life cycle services and manufacturing operates in the same prem-ises. The company's main products are large 4-stroke engines for the marine industry and power plants. The assembly work of the engines is done in assembly cells which consist of cell-specific cranes, height-adjustable assembly platforms, and material supply points. The assembly cells in old premises are not flexible enough and there are safety deficiencies in assembly platforms and when moving to new premises, these problems must be solved. In this thesis design research is used as a research method. The theory part dis-cusses the design of production systems and the consideration of ergonomics in design. The work examines the assembly cell solutions in use at the target company and at competitors. The research focuses on solutions that affect safety, construction, and space in use. In this thesis is created an assembly cell concept and based on the concept is imple-mented three variations of assembly cells with different dimensions. The most important features of the concept are the combination of material feeding and crane structures with a space-saving structure, as well as widely adjustable assembly platforms that can be classified as personal lifts. Assembly platform extension and safety rail solution enable the edges of the generic product to be covered in accordance with EN ISO14122 re-quirements. The developed assembly platform extension and safety rail solution have received positive feedback within the target company, and they have been found to be functional, so they will be used in other locations as well. Dividing the structure into interfaces and using a modular structure reduced design costs by 50 % and made it possible to divide the implementation to different suppliers

pocl: A Performance-Portable OpenCL Implementation

OpenCL is a standard for parallel programming of heterogeneous systems. The benefits of a common programming standard are clear; multiple vendors can provide support for application descriptions written according to the standard, thus reducing the program porting effort. While the standard brings the obvious benefits of platform portability, the performance portability aspects are largely left to the programmer. The situation is made worse due to multiple proprietary vendor implementations with different characteristics, and, thus, required optimization strategies. In this paper, we propose an OpenCL implementation that is both portable and performance portable. At its core is a kernel compiler that can be used to exploit the data parallelism of OpenCL programs on multiple platforms with different parallel hardware styles. The kernel compiler is modularized to perform target-independent parallel region formation separately from the target-specific parallel mapping of the regions to enable support for various styles of fine-grained parallel resources such as subword SIMD extensions, SIMD datapaths and static multi-issue. Unlike previous similar techniques that work on the source level, the parallel region formation retains the information of the data parallelism using the LLVM IR and its metadata infrastructure. This data can be exploited by the later generic compiler passes for efficient parallelization. The proposed open source implementation of OpenCL is also platform portable, enabling OpenCL on a wide range of architectures, both already commercialized and on those that are still under research. The paper describes how the portability of the implementation is achieved. Our results show that most of the benchmarked applications when compiled using pocl were faster or close to as fast as the best proprietary OpenCL implementation for the platform at hand.Comment: This article was published in 2015; it is now openly accessible via arxi

Tips and turns of bacteriophytochrome photoactivation

Phytochromes are ubiquitous photosensor proteins, which control the growth, reproduction and movement in plants, fungi and bacteria. Phytochromes switch between two photophysical states depending on the light conditions. In analogy to molecular machines, light absorption induces a series of structural changes that are transduced from the bilin chromophore, through the protein, and to the output domains. Recent progress towards understanding this structural mechanism of signal transduction has been manifold. We describe this progress with a focus on bacteriophytochromes. We describe the mechanism along three structural tiers, which are the chromophore-binding pocket, the photosensory module, and the output domains. We discuss possible interconnections between the tiers and conclude by presenting future directions and open questions. We hope that this review may serve as a compendium to guide future structural and spectroscopic studies designed to understand structural signaling in phytochromes.Peer reviewe

Conserved histidine and tyrosine determine spectral responses through the water network in Deinococcus radiodurans phytochrome

Funding Information: This work was supported by Academy of Finland grants 285461 (H.T.), 330678 (H.T., J.R.), 277194 (H.L.), and 290677 (S.M.). We acknowledge the European Synchrotron Radiation Facility (ESRF) for providing synchrotron access for crystal data collection. We thank Prof. Janne Ihalainen (University of Jyväskylä) for all the help in all aspects of the paper, Prof. Gerrit Groenhof (University of Jyväskylä) for support, and Prof. Nikolai V. Tkachenko (Tampere University) for help and facilities for time-resolved absorption spectroscopy. We also thank M.Sc. Alli Liukkonen (University of Jyväskylä) and Dr. Heikki Häkkänen (University of Jyväskylä) for the assistance in laboratory and spectroscopy, respectively. Funding Information: This work was supported by Academy of Finland grants 285461 (H.T.), 330678 (H.T., J.R.), 277194 (H.L.), and 290677 (S.M.). We acknowledge the European Synchrotron Radiation Facility (ESRF) for providing synchrotron access for crystal data collection. We thank Prof. Janne Ihalainen (University of Jyväskylä) for all the help in all aspects of the paper, Prof. Gerrit Groenhof (University of Jyväskylä) for support, and Prof. Nikolai V. Tkachenko (Tampere University) for help and facilities for time-resolved absorption spectroscopy. We also thank M.Sc. Alli Liukkonen (University of Jyväskylä) and Dr. Heikki Häkkänen (University of Jyväskylä) for the assistance in laboratory and spectroscopy, respectively. Publisher Copyright: © 2022, The Author(s).Phytochromes are red light-sensing photoreceptor proteins that bind a bilin chromophore. Here, we investigate the role of a conserved histidine (H260) and tyrosine (Y263) in the chromophore-binding domain (CBD) of Deinococcus radiodurans phytochrome (DrBphP). Using crystallography, we show that in the H260A variant, the missing imidazole side chain leads to increased water content in the binding pocket. On the other hand, Y263F mutation reduces the water occupancy around the chromophore. Together, these changes in water coordination alter the protonation and spectroscopic properties of the biliverdin. These results pinpoint the importance of this conserved histidine and tyrosine, and the related water network, for the function and applications of phytochromes.Peer reviewe

Short-term bone biochemical response to a single bout of high-impact exercise

Bone response to a single bout of exercise can be observed with biochemical markers of bone formation and resorption. The purpose of this study was to examine the response of bone biochemical markers to a single bout of exhaustive high-impact exercise. 15 physically active young subjects volunteered to participate. The subjects performed continuous bilateral jumping with the ankle plantarflexors at 65 % of maximal ground reaction force (GRF) until exhaustion. Loading was characterized by analyzing the GRF recorded for the duration of the exercise. Venous blood samples were taken at baseline, immediately after, 2h and on day 1 and day 2 after the exercise. Procollagen type I amino terminal propeptide (P1NP, marker of bone formation) and carboxyterminal crosslinked telopeptide (CTx, marker of bone resorption) were analyzed from the blood samples. CTx increased significantly (32 %, p = 0.015) two days after the exercise and there was a tendensy towards increase seen in P1NP (p = 0.053) one day after the exercise. A significant positive correlation (r = 0.49 to 0.69, p &le; 0.038) was observed between change in P1NP from baseline to day 1 and exercise variables (maximal slope of acceleration, body weight (BW) adjusted maximal GRF, BW adjusted GRF exercise intensity and osteogenic index). Based on the two biochemical bone turnover markers, it can be concluded that bone turnover is increased in response to a very<br /

Conserved histidine and tyrosine determine spectral responses through the water network in Deinococcus radiodurans phytochrome

Phytochromes are red light-sensing photoreceptor proteins that bind a bilin chromophore. Here, we investigate the role of a conserved histidine (H260) and tyrosine (Y263) in the chromophore-binding domain (CBD) of Deinococcus radiodurans phytochrome (DrBphP). Using crystallography, we show that in the H260A variant, the missing imidazole side chain leads to increased water content in the binding pocket. On the other hand, Y263F mutation reduces the water occupancy around the chromophore. Together, these changes in water coordination alter the protonation and spectroscopic properties of the biliverdin. These results pinpoint the importance of this conserved histidine and tyrosine, and the related water network, for the function and applications of phytochromes.</p

Optogenetic Control of Bacterial Expression by Red Light

In optogenetics, as in nature, sensory photoreceptors serve to control cellular processes by light. Bacteriophytochrome (BphP) photoreceptors sense red and farred light via a biliverdin chromophore and, in response, cycle between the spectroscopically, structurally, and functionally distinct Pr and Pfr states. BphPs commonly belong to two-component systems that control the phosphorylation of cognate response regulators and downstream gene expression through histidine kinase modules. We recently demonstrated that the paradigm BphP from Deinococcus radiodurans exclusively acts as a phosphatase but that its photosensory module can control the histidine kinase activity of homologous receptors. Here, we apply this insight to reprogram two widely used setups for bacterial gene expression from blue-light to red-light control. The resultant pREDusk and pREDawn systems allow gene expression to be regulated down and up, respectively, uniformly under red light by 100-fold or more. Both setups are realized as portable, single plasmids that encode all necessary components including the biliverdin-producing machinery. The triggering by red light affords high spatial resolution down to the single-cell level. As pREDusk and pREDawn respond sensitively to red light, they support multiplexing with optogenetic systems sensitive to other light colors. Owing to the superior tissue penetration of red light, the pREDawn system can be triggered at therapeutically safe light intensities through material layers, replicating the optical properties of the skin and skull. Given these advantages, pREDusk and pREDawn enable red-light-regulated expression for diverse use cases in bacteria.Peer reviewe

On the (un)coupling of the chromophore, tongue interactions, and overall conformation in a bacterial phytochrome

Phytochromes are photoreceptors in plants, fungi, and various microorganisms and cycle between metastable red light-absorbing (Pr) and far-red light-absorbing (Pfr) states. Their light responses are thought to follow a conserved structural mechanism that is triggered by isomerization of the chromophore. Downstream structural changes involve refolding of the so-called tongue extension of the phytochrome-specific GAF-related (PHY) domain of the photoreceptor. The tongue is connected to the chromophore by conserved DIP and PRXSF motifs and a conserved tyrosine, but the role of these residues in signal transduction is not clear. Here, we examine the tongue interactions and their interplay with the chromophore by substituting the conserved tyrosine (Tyr(263)) in the phytochrome from the extremophile bacterium Deinococcus radiodurans with phenylalanine. Using optical and FTIR spectroscopy, X-ray solution scattering, and crystallography of chromophore-binding domain (CBD) and CBD-PHY fragments, we show that the absence of the Tyr(263) hydroxyl destabilizes the -sheet conformation of the tongue. This allowed the phytochrome to adopt an -helical tongue conformation regardless of the chromophore state, hence distorting the activity state of the protein. Our crystal structures further revealed that water interactions are missing in the Y263F mutant, correlating with a decrease of the photoconversion yield and underpinning the functional role of Tyr(263) in phytochrome conformational changes. We propose a model in which isomerization of the chromophore, refolding of the tongue, and globular conformational changes are represented as weakly coupled equilibria. The results also suggest that the phytochromes have several redundant signaling routes.Peer reviewe