923 resultados para CRITICAL ORGANS
Resumo:
In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.
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In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.
Resumo:
Nykyaikaisessa liiketoimintaympäristössä yritysten kriittisiksi resursseiksi ovat muodostuneet liiketoimintaa tukevat tietojärjestelmät. Mahdollisuus hyödyntää näitä resursseja riippuu ko. liiketoiminnalle kriittisten järjestelmien luotettavuudesta ja hyödynnettävien sovellusten saatavuudesta. Eräs tilanne jossa järjestelmien kyky tukea todellisia liiketoimintaprosesseja vaarantuu on katastrofi. Vaikutukseltaan katastrofi voi olla paikallinen tai kattaa laajojakin alueita. Eri tyyppisiin katastrofeihin on varauduttava niiden edellyttämin tavoin. Eräs kriittisten tietojärjestelmien arkkitehtuuriin vaikuttanut trendi 90-luvulla on ollut client/server lähestymistapa. Client/server paradigman mukaan sovellus jaetaan tasoihin siten että esitys-, sovellus- ja tietokantakerrokset voidaan erottaa fyysisesti toisistaan näiden silti muodostaessa loogisesti yhtenäisen kokonaisuuden. Liiketoiminnan näkökulmasta 90- luvun mullistavia IT-uutuuksia olivat toiminnanohjausjärjestelmät, joiden avulla oli mahdollista hallita koko tuotantoketjua ja muita prosessikokonaisuuksia lähes reaaliajassa. Monikerroksisten toiminnanohjausjärjestelmien luotettavuus on osoittautunut haastavavaksi sillä kaikkien kerrosten suojaaminen kaikilta mahdollisilta katastrofeilta täydellisesti on nykyisellä teknologialla mahdotonta. Kompromissien tekemiseksi on oltava selvillä kunkin menetetyn prosessin aiheuttamista taloudellisista ja liiketoiminnallisista vaikutuksista. Tämän vuoksi juuri toiminnanohjausjärjestelmät ovat mielenkiintoisia, vaikuttavathan ne liiketoimintaprosesseihin läpi koko yrityksen prosessiketjun. Monikerroksisten client/server arkkitehtuuriin pohjautuvien toiminnanohjausjärjestelmien suojaamisessa katastrofeilta onkin sovellettava useita tekniikoita ja teknologioita, ja yhdistettävä kokonaisuus prosessikehykseen. Näin voidaan luoda suunnitelmallinen osa IT strategiaa, joka ottaa kantaa liiketoiminnan jatkuvuuteen katastrofitilanteessa ja mahdollistaa nopean ja täydellisen palautumisen kaikissa olosuhteissa.
Resumo:
Työn pääasiallisena tavoitteena on selvittää ydinosaamista, jota tarvitaan kansainvälisen metsäteollisuusyrityksen loppukäyttäjävetoisessa liiketoiminnassa. Lisäksi tavoitteena on laatia kompetenssimalli, jota voidaan käyttää mm. rekrytoinnissa, koulutuksen ja työnkierron suunnittelussa. Tarkoituksena on tarkastella sekä tällä hetkellä että tulevaisuudessa tarvittavia ydinosaamisia. Työ keskittyy myyntihenkilöiden kompetenssien kuvaamiseen. Kirjallisuuden ja asiantuntijoiden haastattelujen avulla on selvitetty. kompetensseihin liittyviä asioita ja käsitteitä, kuten organisaation oppiminen, innovaatiot sekä asiakaslähtöisyys. Tämän jälkeen on kartoitettu case-yrityksen kartonkiyksikön myyntihenkilökunnan kompetensseja. Kompetenssikartoitus on tehty teemahaastattelujen avulla sekä lisäksi on käytetty työn aikana laadittua kompetenssimatriisia. Saatuja tuloksia on verrattu yhden asiakkaan näkemyksiin. Tulosten mukaan kolme tärkeintä tämän hetken kompetenssia ovat: holistinen näkemys asioista, suhteiden rakentaminen ja kielitaito. Tulevaisuuden tärkeimpiä kompetensseja puolestaan ovat: asiakaslähtöisyys, sähköinen kaupankäynti ja suhteiden rakentaminen. Lopuksi on käsitelty yleisiä metsäteollisuuden tulevaisuuden haasteita sekä annettu joitain kehitysideoita kompetenssien kehittämistä varten.
Resumo:
Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.
Resumo:
Gene turnover rates and the evolution of gene family sizes are important aspects of genome evolution. Here, we use curated sequence data of the major chemosensory gene families from Drosophila-the gustatory receptor, odorant receptor, ionotropic receptor, and odorant-binding protein families-to conduct a comparative analysis among families, exploring different methods to estimate gene birth and death rates, including an ad hoc simulation study. Remarkably, we found that the state-of-the-art methods may produce very different rate estimates, which may lead to disparate conclusions regarding the evolution of chemosensory gene family sizes in Drosophila. Among biological factors, we found that a peculiarity of D. sechellia's gene turnover rates was a major source of bias in global estimates, whereas gene conversion had negligible effects for the families analyzed herein. Turnover rates vary considerably among families, subfamilies, and ortholog groups although all analyzed families were quite dynamic in terms of gene turnover. Computer simulations showed that the methods that use ortholog group information appear to be the most accurate for the Drosophila chemosensory families. Most importantly, these results reveal the potential of rate heterogeneity among lineages to severely bias some turnover rate estimation methods and the need of further evaluating the performance of these methods in a more diverse sampling of gene families and phylogenetic contexts. Using branch-specific codon substitution models, we find further evidence of positive selection in recently duplicated genes, which attests to a nonneutral aspect of the gene birth-and-death process.
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Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle) 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in"other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the"rest" of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed.
Resumo:
By means of computer simulations and solution of the equations of the mode coupling theory (MCT),we investigate the role of the intramolecular barriers on several dynamic aspects of nonentangled polymers. The investigated dynamic range extends from the caging regime characteristic of glass-formers to the relaxation of the chain Rouse modes. We review our recent work on this question,provide new results, and critically discuss the limitations of the theory. Solutions of the MCT for the structural relaxation reproduce qualitative trends of simulations for weak and moderate barriers. However, a progressive discrepancy is revealed as the limit of stiff chains is approached. This dis-agreement does not seem related with dynamic heterogeneities, which indeed are not enhanced by increasing barrier strength. It is not connected either with the breakdown of the convolution approximation for three-point static correlations, which retains its validity for stiff chains. These findings suggest the need of an improvement of the MCT equations for polymer melts. Concerning the relaxation of the chain degrees of freedom, MCT provides a microscopic basis for time scales from chain reorientation down to the caging regime. It rationalizes, from first principles, the observed deviations from the Rouse model on increasing the barrier strength. These include anomalous scaling of relaxation times, long-time plateaux, and nonmonotonous wavelength dependence of the mode correlators.
Resumo:
G protein-gated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which reduces surface expression of GIRK channels through a PDZ domain interaction, contains a putative Ras-association (RA) domain with unknown function. Deleting the RA domain in SNX27b (SNX27b-DRA) prevents the down-regulation of GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro. Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a functional RA domain and the interaction with Ras-like G proteins comprise a novel mechanism for modulating SNX27b control of GIRK channel surface expression and cellular excitability.
Resumo:
Työn tavoitteena oli kartonkivuoan kriittisten menestystekijöiden ja kilpailuaseman selvittäminen jäähdytettyjen ruokatuotteiden markkinoilla Euroopassa. Kilpailija- ja tavoiteanalyysi suoritettiin kahden suomalaisen pakkaajan kesken. Pakkaajien haastattelut toteutettiin joko henkilökohtaisena tai sähköpostihaastatteluna. Muovi on yleisimmin käytetty jäähdytettyjen ruokatuotteiden pakkausmateriaali. Alumiinivuokien osuus on merkittävä erityisesti laatikkoruokien pakkauksena. Kartonkivuoille on kuitenkin havaittavissa selvää menestyspotentiaalia jäähdytettyjen ruokien pakkauksena. Kartonkivuokien hyvä imago ja edistyksellinen tuotekehitystyö mahdollistavat pakkaajien erityisvaatimuksien täyttämisen ja menestymisen markkinoilla. Kartonkivuoilla on useita ainutlaatuisia kilpailuetu- ja menestystekijöitä, kuten hyvä ulkonäkö ja painojälki. Suurin haaste on saada ruokatuotteiden pakkaajat tietoisiksi kartonkivuokien tuomista pakkausmahdollisuuksista.
Resumo:
Tyon tavoitteena on selvittaa. mitka myyntistrategian ja siihen liittyvien muiden strategioiden kriittiset osat pienten ja keskisuurten ICT- yritysten toiminnassa. Tutkimusmenetelmana kaytettiin case- tutkimusta, jossa vertailtiin neljan pienen ja keskisuuren ohjelmisto talon toimintaa. Tutkimuksessa tunnistettiin nelja kriittista osa-aluetta, joiden hoitamiseen yritysten erityisesti tulisi kiinnittaa huomiota. Nama olivat: segmentointi ja kohdemarkkinoiden valinta, myyntikanavien valinta, myyntihenkiloston organisointi ja asiakassuuntautuneisuus, ja markkinointi tietojarjestelma. Tutkimus osoitti, etta yrityksen kasvaessa ja omistuksen eriytyessa toimivasta johdosta yrityksen strategia suunnittelusta tulee jarjestelmallisempaa.
Resumo:
The purpose of this contribution is to analyse the trajectory, the challenges and the future of the sociology of sport on three levels: the internal dynamic within the specific sub-field of the sociology of sport, its interactions with sociology and sport sciences, and its relation with sport organizations. The paper notes that the changes of the trajectory of the sociology of sport, first leaning on the profession of physical education teacher and then to sport sciences, as important consequences. Because most of the sociologists specialized in sport are working in sport sciences departments, the most important consequence is the dependency on sport sciences rather than on sociology. Compared to other fields of sociology, it means challenging other sciences for recognition. The paper argues that to face the threat of a marginalization within the field of sport science, the future of sociology of sport could be to fight for an external recognition. Applying sociology could spread critical views that are necessary to sport organizations. It could also give sociologists access to very interesting data, which can help producing good research, and give it a greater legitimacy within sport sciences. However, it is a risky strategy because of the necessity for the sociologists to stay critical both on sporting organization and on their own work.
Resumo:
BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.
Resumo:
The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.