999 resultados para internal target


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Tämän kandidaatintyön tavoitteena on tarkastella suorien ulkomaisten investointien kehittymistä Venäjällä Neuvostoliiton romahtamisen jälkeen sekä selvittää niihin vaikuttaneita Venäjän sisäisiä tekijöitä. Tarkastelu toteutetaan ulkomaisten sijoittajien näkökulmasta. Työ rakentuu kolmesta osiosta, joista ensimmäisessä esitellään suoriin ulkomaisiin investointeihin liittyvää perustietoutta. Toisessa osassa keskitytään Venäjän historiaan ja niihin talousindikaattoreihin, jotka vaikuttavat merkittävimmin maahan investoimiseen. Kolmannessa osassa paneudutaan suorien ulkomaisten investointien kehitysprofiiliin ja siihen, kuinka investoinnit jakautuvat maassa eri toimialojen kesken sekä myös maantieteellisesti. Analyysien perusteella luodaan katsaus tulevaisuuteen, joka näyttää Venäjälle suuntautuvien suorien ulkomaisten investointien osalta suopealta, mutta joskin myös haastavalta. Venäjä vaikuttaa olevan sijoituskohteena lupaava ulkomaisille yrityksille, joiden tavoitteena on laajentaa markkinoitaan, sillä ostovoima kasvu on maassa merkittävä. Toisaalta Venäjälle investoiminen saattaa tuoda yritysten eteen yllättäviäkin haasteita.

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Irrigated agriculture has come under close scrutiny in Europe recently because of its high share of total water consumption and its apparent inefficiency. Several water policies have been advocated, in particular the use of economic instruments such as water markets. This paper simulates the impact of a policy based upon water markets on agricultural production in the internal river basins of Catalonia (Spain). This zone presents certain particularities that make it very interesting to study: competition between sectors for the resource (agriculture-urban consumption-recreational uses), recent periods of resource insufficiency and conflicts between irrigators as a result of the measures taken by the hydraulic administration in drought situations. The results show that these markets would guarantee an optimal reassignment of the resource in situations of supply restrictions, and although compared to the situation without markets they would not mean higher economic profits for the irrigators, they could prevent conflicts between them. Nevertheless, doubts exist about their acceptance by irrigators

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Tilintarkastuksen kohteina ovat yhteisön tai säätiön tilikauden kirjanpidon ja tilinpäätöksen sekä hallinnon tarkastus. Konsernin tilintarkastajan on myös tarkastettava emoyrityksenä olevan yhteisön tai säätiön laatima konsernitilinpäätös sekä konserniin kuuluvien yhteisöjen ja säätiön keskinäisiä suhteita. Tämän tutkimuksen tavoitteena on kartoittaa ja analysoida konsernin tilintarkastuksen ongelmakohtia kohdeyrityksen näkökulmasta sekä analysoida tilintarkastuslain uudistuksen vaikutuksia ongelmiin. Tutkimuksessa hahmotetaan ensin konsernin tilintarkastuksen aihepiiriä kirjallisuuden pohjalta. Empiirisessä osuudessa tutkitaan teemahaastattelujen avulla konserniympäristön tilintarkastusprosessia ja lopuksi peilataan kohdeyrityksen näkemystä tilintarkastuksen doktriiniin. Tutkimus osoittaa konsernin tarkastusprosessiin osallistuvien osapuolten yhteistyön merkittäväksi tekijäksi ongelmien ehkäisemisessä. Tilintarkastuslain uudistuksella ei ollut vaikutusta kohdeyrityksen näkemyksen mukaisiin ongelmakohtiin.

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The main target of the study was to examine how Fortum’s tax reporting system could be developed in a way that it collects required information which is also easily transferable to the financial statements. This included examining disclosure requirements for income taxes under IFRS and US GAAP. By benchmarking some Finnish, European and US companies the purpose was to get perspective in what extend they present their tax information in their financial statements. Also material weakness, its existence, was under examination. The research method was qualitative, descriptive and normative. The research material included articles and literature of the tax reporting and standards relating to it. The interviews made had a notable significance. The study pointed out that Fortum’s tax reporting is in good shape and it does not require big changes. The biggest renewal of the tax reporting system is that there is only one model for all Fortum’s companies. It is also more automated, quicker, and more efficient and it reminds more the notes in its shape. In addition it has more internal controls to improve quality and efficiency of the reporting process.

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Tutkimuksen tavoitteena oli tapaustutkimuksen avulla analysoida ja kehittää case-organisaation siirtohinnoittelua ja siirtohinnoitteludokumentointia. Siirtohinnoittelun osalta analysoitiin tarkoitus, motiivi, vaikuttavat tekijät, tekniikka ja tavoitteet. Kun siirtohinnoittelu avaintekijät saatiin selvitettyä, keskityttiin siirtohinnoittelun dokumentointiin ja erityisesti siirtohinnoittelumenetelmien analysoitiin. Tutkielman teoriaosassa analysoitiin siirtohinnoittelua ja siirtohinnoitteludokumentointia käsittelevää kirjallisuutta ja tutkimuksia. Empiirisen osion aineisto kerättiin haastattelemalla, tutustumalla kohdeyrityksen dokumentteihin ja tietojärjestelmiin sekä osallistuvalla havainnoinnilla. Tutkielman empiirisessä osiossa tarkasteltiin kohdeyrityksen siirtohinnoittelua ja siirtohinnoitteludokumentointia. Tulokseksi saatiin, että sisäiset ohjeet, liiketoiminnalliset ja strategiset tavoitteet vaikuttivat eniten siirtohinnoitteluun. Jatkossa kohdeyrityksen tulisi kiinnittää enemmän huomiota siirtohinnoittelussaan kapasiteetteihin ja niistä aiheutuviin kustannuksiin. Kohdeyritys ei ole aikaisemmin suorittanut siirtohinnoitteludokumentointia. Siirtohinnoitteludokumentoinnin toteuttaminen on mahdollista saatujen tutkimustulosten avulla. Kustannusvoittolisämenetelmä on parhaiten kohdeyritykselle soveltuva siirtohinnoittelumenetelmä.

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INTERMED training implies a three week course, integrated in the "primary care module" for medical students in the first master year at the school of medicine in Lausanne. INTERMED uses an innovative teaching method based on repetitive sequences of e-learning-based individual learning followed by collaborative learning activities in teams, named Team-based learning (TBL). The e-learning takes place in a web-based virtual learning environment using a series of interactive multimedia virtual patients. By using INTERMED students go through a complete medical encounter applying clinical reasoning and choosing the diagnostic and therapeutic approach. INTERMED offers an authentic experience in an engaging and safe environment where errors are allowed and without consequences.

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A group of family physicians in an outpatient clinic in Switzerland prospectively followed scientific literature for ten years. What to remember among the numerous articles retrieved and which paper really changed our practice? If many readings are quickly forgotten, some of them marked our minds and changed our habits. This article is a summary of our efforts to keep the essential tools in clinical practice.

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The objective of the thesis was to explore the nature and characteristics of customer-related internal communication in a global industrial matrix organization during a specific customer relationship, and how it could be improved. The theoretical part of the study views the field of the concepts of intra-organizational information and knowledge sharing. The theoretical part also views the internal communications influences to customer relationships, its problematic, and the suggestions to improve internal communication in literature. The empirical part of the study was conducted with the Content Analysis and the Social Network Analysis as research methods. The data was collected by interviews and a questionnaire. Internal communication was observed first generally within the organization from the point of view of a certain business, and secondly, during a specific customer relationship at personal level and at departmental level. The results of the study describe the nature and characteristics of internal communication in the organization. The results give 13 suggestions for improving internal communication in the organization. Although the study has been done in one specific organization, it also offers insights for other organizations as well as managers to improve their internal communication.

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The present work describes the development of a fast and robust analytical method for the determination of 53 antibiotic residues, covering various chemical groups and some of their metabolites, in environmental matrices that are considered important sources of antibiotic pollution, namely hospital and urban wastewaters, as well as in river waters. The method is based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UHPLC–QqLIT). For unequivocal identification and confirmation, and in order to fulfill EU guidelines, two selected reaction monitoring (SRM) transitions per compound are monitored (the most intense one is used for quantification and the second one for confirmation). Quantification of target antibiotics is performed by the internal standard approach, using one isotopically labeled compound for each chemical group, in order to correct matrix effects. The main advantages of the method are automation and speed-up of sample preparation, by the reduction of extraction volumes for all matrices, the fast separation of a wide spectrum of antibiotics by using ultra-high-performance liquid chromatography, its sensitivity (limits of detection in the low ng/L range) and selectivity (due to the use of tandem mass spectrometry) The inclusion of β-lactam antibiotics (penicillins and cephalosporins), which are compounds difficult to analyze in multi-residue methods due to their instability in water matrices, and some antibiotics metabolites are other important benefits of the method developed. As part of the validation procedure, the method developed was applied to the analysis of antibiotics residues in hospital, urban influent and effluent wastewaters as well as in river water samples

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Trying to define the precise role played by insulin regulating the survival of brown adipocytes, we have used rat fetal brown adipocytes maintained in primary culture. The effect of insulin on apoptosis and the mechanisms involved were assessed. Different from the known effects of insulin as a survival factor, we have found that long-term treatment (72 h) with insulin induces apoptosis in rat fetal brown adipocytes. This process is dependent on the phosphatidylinositol 3-kinase/mammalian target of rapamycin/p70 S6 kinase pathway. Short-term treatment with the conditioned medium from brown adipocytes treated with insulin for 72 h mimicked the apoptotic effect of insulin. During the process, caspase 8 activation, Bid cleavage, cytochrome c release, and activation of caspases 9 and 3 are sequentially produced. Treatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Z-VAD), prevents activation of this apoptotic cascade. The antioxidants, ascorbic acid and superoxide dismutase, also impair this process of apoptosis. Moreover, generation of reactive oxygen species (ROS), probably through reduced nicotinamide adenine dinucleotide phosphate oxidases, and a late decrease in reduced glutathione content are produced. According to this, antioxidants prevent caspase 8 activation and Bid cleavage, suggesting that ROS production is an important event mediating this process of apoptosis. However, the participation of uncoupling protein-1, -2, and -3 regulating ROS is unclear because their levels remain unchanged upon insulin treatment for 72 h. Our data suggest that the prolonged hyperinsulinemia might cause insulin resistance through the loss of brown adipose tissue.

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How to recognize, announce and analyze incidents in internal medicine units is a daily challenge that is taught to all hospital staff. It allows suggesting useful improvements for patients, as well as for the medical department and the institution. Here is presented the assessment made in the CHUV internal medicine department one year after the beginning of the institutional procedure which promotes an open process regarding communication and risk management. The department of internal medicine underlines the importance of feedback to the reporters, ensures the staff of regular follow-up concerning the measures being taken and offers to external reporters such as general practioners the possibility of using this reporting system too.

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The year 2014 was rich in significant advances in all areas of internal medicine. Many of them have an impact on our daily practice and on the way we manage one problem or another. From the use of the ultrasound for the diagnosis of pneumonia to the choice of the site of venous access and the type of line, and the increasing complexity of choosing an oral anticoagulant agent, this selection offers to the readers a brief overview of the major advances. The chief residents in the Service of internal medicine of the Lausanne University hospital are pleased to share their readings.

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L'ARN polymérase 3 transcrit un petit groupe de gènes fortement exprimés et impliqués dans plusieurs mécanismes moléculaires. Les ARNs de transfert ou ARNt représentent plus ou moins la moitié du transcriptome de l'ARN polymérase 3. Ils sont directement impliqués dans la traduction des protéines en agissant comme transporteurs d'acides aminés qui sont incorporés à la chaîne naissante de polypeptides. Chez des levures cultivées dans un milieu jusqu'à épuisement des nutriments, Maf1 réprime la transcription par l'ARN polymérase 3, favorisant ainsi l'économie énergétique cellulaire. Dans un modèle de cellules de mammifères, MAF1 réprime aussi la transcription de l'ARN polymérase 3 dans des conditions de stress, cependant il n'existe aucune donnée quant à son rôle chez un mammifère vivant. Pendant mon doctorat, j'ai utilisé une souris délétée pour le gène Maf1 afin de connaître les effets de ce gène chez un mammifère. Etonnamment, la souris Maf1-­‐/-­‐ est résistante à l'obésité même si celle-­‐ci est nourrie avec une nourriture riche en matières grasses. Des études moléculaires et de métabolomiques ont montré qu'il existe des cycles futiles de production et dégradation des lipides et des ARNt, ce qui entraîne une augmentation de la dépense énergique et favorise la résistance à l'obésité. En plus de la caractérisation de la souris Maf1-­‐/-­‐, pendant ma thèse j'ai également développé une méthode afin de normaliser les données de ChIP-­‐sequencing. Cette méthode est fondée sur l'utilisation d'un contrôle interne, représenté ici par l'ajout d'une quantité fixe de chromatine provenant d'un organisme différent de celui étudié. La méthode a amélioré considérablement la reproductibilité des valeurs entre réplicas biologiques. Elle a aussi révélé des différences entre échantillons issus de conditions différentes. Une occupation supérieure de l'ARN polymérase 3 sur les gènes Pol 3 chez les souris Maf1 KO entraîne une augmentation du niveau de précurseurs d'ARNt, ayant pour effet probable la saturation de la machinerie de maturation des ARNt. En effet, chez les souris Maf1 KO, le pourcentage d'ARNt modifiés est plus faible que chez les souris type sauvage. Ce déséquilibre entre le niveau de précurseurs et d'ARNt matures entraîne une diminution de la traduction protéique. Ces résultats ont permis d'identifier de nouvelles fonctions pour la protéine MAF1, comme étant une protéine régulatrice à la fois de la transcription mais aussi de la traduction et en étant un cible potentielle au traitement à l'obésité. -- RNA polymerase III (Pol 3) transcribes a small set of highly expressed genes involved in different molecular mechanisms. tRNAs account for almost half of the Pol 3 transcriptome and are involved in translation, bringing a new amino into the nascent polypeptide chain. In yeast, under nutrient deprivation, Maf1 acts for cell energetic economy by repressing Pol 3 transcription. In mammalian cells, MAF1 also represses Pol 3 activity under conditions of serum deprivation or DNA damages but nothing is known about its role in a mammalian organism. During my thesis studies, I used a Maf1 KO mouse model to characterize the effects of Maf1 deletion in a living animal. Surprisingly, the MAF1 KO mouse developed an unexpected phenotype, being resistant to high fat diet-­‐induced obesity and displaying an extended lifespan. Molecular and metabolomics characterizations revealed futile cycles of lipids and tRNAs, which are produced and immediately degraded, which increases energy consumption in the Maf1 KO mouse and probably explains in part the protection to obesity. Additionally to the mouse characterization, I also developed a method to normalize ChIP-­‐seq data, based on the addition of a foreign chromatin to be used as an internal control. The method improved reproducibility between replicates and revealed differences of Pol 3 occupancy between WT and Maf1 KO samples that were not seen without normalization to the internal control. I then established that increased Pol 3 occupancy in the Maf1 KO mouse liver was associated with increased levels of tRNA precursor but not of mature tRNAs, the effective molecules involved in translation. The overproduction of precursor tRNAs associated with the deletion of Maf1 apparently overwhelms the tRNA processing machinery as the Maf1 KO mice have lower levels of fully modified tRNAs. This maturation defect directly impacts on translation efficiency as polysomic fractions and newly synthetized protein levels were reduced in the liver of the Maf1 KO mouse. Altogether, these results indicate new functions for MAF1, a regulator of both transcription and translation as well as a potential target for obesity treatment.

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Introduction. If we are to promote more patient-centred approaches in care delivery, we have to better characterize the situations in which being patient-centred is difficult to achieve. Data from professionals in health and social care are important because they are the people charged with operationalizing patient-centred care (PCC) in their daily practice. However, empirical accounts from frontline care providers are still lacking, and it is important to gather experiences not only from doctors but also from the other care providers. Indeed, experiences from different professions can help inform our understanding of patient care, which is expected to be both patient-centred and collaborative. Methods. This study was based on the following research question: What factors make the provision of PCC difficult to achieve? Sample and setting. A purposeful sampling technique was used, allowing for a series of choices about the participants and their professional affiliation. Because patient-centredness is the focus, 3 professions appeared to be of special interest: general internists, nurses and social workers. The study was undertaken in the General Internal Medicine Division of a teaching hospital located in a North American context. Data Collection. To answer the research question, a methodological approach based on a theory called phenomenology was chosen. Accordingly, semi-structured interviews were used since they generate understanding of the meanings different individuals have of their lived world. Interviews with 8 physicians, 10 nurses and 10 social workers were eventually conducted. Data analysis. An inductive thematic analysis was employed to make sense of the interview data. Results. The thematic analysis allowed identifying various types of challenges to PCC. Although most of the challenges were perceived by all three groups of professionals, they were perceived to a different degree across the professions, which likely reflected the scope of practice of each profession. The challenges and their distribution across the professions are illustrated in Table 1. Examples of challenges are provided in Table 2. Discussion. There is a tension between what is supposed to be done - what stands in the philosophy of patient -centredness - and what is currently done - the real life with all the challenges to PCC. According to some participants' accounts, PCC clearly risks becoming a mere illusion for health care professionals on which too great pressures are imposed.

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Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment. Rictor deficiency favors memory formation and increases IL-2 secretion capacity without dampening effector functions. Moreover, mTORC2-deficient memory T cells mount more potent recall responses. Enhanced memory formation in the absence of mTORC2 was associated with Eomes and Tcf-1 upregulation, repression of T-bet, enhanced mitochondrial spare respiratory capacity, and fatty acid oxidation. This transcriptional and metabolic reprogramming is mainly driven by nuclear stabilization of Foxo1. Silencing of Foxo1 reversed the increased MPEC differentiation and IL-2 production and led to an impaired recall response of Rictor KO memory T cells. Therefore, mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions.