955 resultados para the accumulation of costs


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Finnish food producers' trade with Russia has experienced profound changes since the collapse of the Soviet Union. Simultaneously, the distribution systems of foodstuffs have changed remarkably. This study sheds some light into these changes and analyses the current situation in distribution systems of foodstuffs in Russia. In addition, the study discusses the possibilities of Finnish food producers to get more of their products to the shelves of Russian food retail stores. Before the 1998 financial crisis, the import of foreign foodstuffs was booming in Russia due to the overvalued rouble. As a result of the financial crisis, food import collapsed. The export of Finnish foodstuffs to Russia has been slowly recovering during the past few years, but in the most important product categories the pre-crisis levels have so far not been reached and maybe will not be reached. In certain product categories the growth has been only marginal. It seems that starting localproduction will become increasingly important in the future. This is further encouraged by the fact that Russian consumers favour domestic food products. Russian consumers are very price conscious and demand quality in food products. The perceived price-quality ratio is an important criterion in the purchase decision.The majority of foodstuff retail is still conducted via unorganised forms of trade (e.g. kiosks and marketplaces) but modern retail chains are developing at a fast pace in Russia. They are also expected to dominate the retail trade in foodstuffs over the unorganised forms of trade in the future. This will change the distribution systems as well. The retail chains are trying to shorten the distribution chain, similarly to what has been seen in the Western countries. This together with the strengthening of retail chains is likely to shrink the role of wholesalers, as the chains increasingly want to work directly with the producers. Many large retail chains are acquiring or have already acquired a distribution centre or centres in order to boost efficiency and control the flow of products. The strengthening of the retail chains also gives them power in negotiations, which the producers and distributors have to adjust to. For example store entry fees and retail chains' own private label products pose challenges to the food producers. In the food production sector the competition is fierce, as large Russianand foreign producers want to ensure their piece of the market. The largest producers utilise their size: they invest in big marketing campaigns and are willing to pay high entry fees to retail chains in order to secure a place on the store shelves and to build a strong brand in Russia. This complicates the situation from the viewpoint of small producers. Currently, the most popular type of distribution system among the interviewed Finnish food producers is based on a network of local distributors. There is, however, a strong consensus on the importanceof starting local production in order to be a serious actor in Russia in the future. Factors that hinder the starting of local production include the lack of local infrastructure and qualified staff, and the low risk tolerance of Finnish firms. Major barriers for entry in Russia are the actions of authorities, fierce competition, fragmented market and Finnish producers' heavy production costs. The suggested strategies for increasing the market share include focusing geographically or segment-wise, introducing new products, starting local production, andcooperation between Finnish producers. Smallness was one reason why Finnish producers had to cut down their operations in Russia due to the 1998 crisis. Smaller producers had fewer resources to tolerate losses during the period of crisis. Smallness is reflected also on trade negotiations with retail chains and distributors. It makes it harder to cope with the store entry fees and to differentiatefrom the mass of products propped up by expensive advertising. Finally, it makes it harder for Finnish producers to start or expand local production, as it is more difficult for a small producer to get financing and to tolerate the increased risks. Compensating for the smallness might become the crucial factor determining the future success of Finnish food producers in the Russian market.

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Productivity and profitability are important concepts and measures describing the performance and success of a firm. We know that increase in productivity decreases the costs per unit produced and leads to better profitability. This common knowledge is not, however, enough in the modern business environment. Productivity improvement is one means among others for increasing the profitability of actions. There are many means to increase productivity. The use of these means presupposes operative decisions and these decisions presuppose informationabout the effects of these means. Productivity improvement actions are in general made at floor level with machines, cells, activities and human beings. Profitability is most meaningful at the level of the whole firm. It has been very difficult or even impossible to analyze closely enough the economical aspects of thechanges at floor level with the traditional costing systems. New ideas in accounting have only recently brought in elements which make it possible to considerthese phenomena where they actually happen. The aim of this study is to supportthe selection of objects to productivity improvement, and to develop a method to analyze the effects of the productivity change in an activity on the profitability of a firm. A framework for systemizing the economical management of productivity improvement is developed in this study. This framework is a systematical way with two stages to analyze the effects of productivity improvement actions inan activity on the profitability of a firm. At the first stage of the framework, a simple selection method which is based on the worth, possibility and the necessity of the improvement actions in each activity is presented. This method is called Urgency Analysis. In the second stage it is analyzed how much a certain change of productivity in an activity affects the profitability of a firm. A theoretical calculation model with which it is possible to analyze the effects of a productivity improvement in monetary values is presented. On the basis of this theoretical model a tool is made for the analysis at the firm level. The usefulness of this framework was empirically tested with the data of the profit center of one medium size Finnish firm which operates in metal industry. It is expressedthat the framework provides valuable information about the economical effects of productivity improvement for supporting the management in their decision making.

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Intrinsic resistance to the epidermal growth factor receptor (EGFR; HER1) tyrosine kinase inhibitor (TKI) gefitinib, and more generally to EGFR TKIs, is a common phenomenon in breast cancer. The availability of molecular criteria for predicting sensitivity to EGFR-TKIs is, therefore, the most relevant issue for their correct use and for planning future research. Though it appears that in non-small-cell lung cancer (NSCLC) response to gefitinib is directly related to the occurrence of specific mutations in the EGFR TK domain, breast cancer patients cannot be selected for treatment with gefitinib on the same basis as such EGFR mutations have beenreported neither in primary breast carcinomas nor in several breast cancer cell lines. Alternatively, there is a generalagreement on the hypothesis that the occurrence of molecular alterations that activate transduction pathways downstreamof EGFR (i.e., MEK1/MEK2 - ERK1/2 MAPK and PI-3'K - AKT growth/survival signaling cascades) significantly affect the response to EGFR TKIs in breast carcinomas. However,there are no studies so far addressing a role of EGF-related ligands as intrinsic breast cancer cell modulators of EGFR TKIefficacy. We recently monitored gene expression profiles andsub-cellular localization of HER-1/-2/-3/-4 related ligands (i.e., EGF, amphiregulin, transforming growth factor-α, ß-cellulin,epiregulin and neuregulins) prior to and after gefitinib treatment in a panel of human breast cancer cell lines. First, gefitinibinduced changes in the endogenous levels of EGF-related ligands correlated with the natural degree of breast cancer cellsensitivity to gefitinib. While breast cancer cells intrinsically resistant to gefitinib (IC50 ≥15 μM) markedly up-regulated(up to 600 times) the expression of genes codifying for HERspecific ligands, a significant down-regulation (up to 106 times)of HER ligand gene transcription was found in breast cancer cells intrinsically sensitive to gefitinib (IC50 ≤1 μM). Second,loss of HER1 function differentially regulated the nuclear trafficking of HER-related ligands. While gefitinib treatment induced an active import and nuclear accumulation of the HER ligand NRG in intrinsically gefitinib-resistant breastcancer cells, an active export and nuclear loss of NRG was observed in intrinsically gefitinib-sensitive breast cancer cells.In summary, through in vitro and pharmacodynamic studies we have learned that, besides mutations in the HER1 gene,oncogenic changes downstream of HER1 are the key players regulating gefitinib efficacy in breast cancer cells. It now appears that pharmacological inhibition of HER1 functionalso leads to striking changes in both the gene expression and the nucleo-cytoplasmic trafficking of HER-specific ligands,and that this response correlates with the intrinsic degree of breast cancer sensitivity to the EGFR TKI gefitinib. Therelevance of this previously unrecognized intracrine feedback to gefitinib warrants further studies as cancer cells could bypassthe antiproliferative effects of HER1-targeted therapeutics without a need for the overexpression and/or activation of other HER family members and/or the activation of HER-driven downstream signaling cascades

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Yeast cells contain a family of three monothiol glutaredoxins: Grx3, 4, and 5. Absence of Grx5 leads to constitutive oxidative damage, exacerbating that caused by external oxidants. Phenotypic defects associated with the absence of Grx5 are suppressed by overexpression ofSSQ1 and ISA2, two genes involved in the synthesis and assembly of iron/sulfur clusters into proteins. Grx5 localizes at the mitochondrial matrix, like other proteins involved in the synthesis of these clusters, and the mature form lacks the first 29 amino acids of the translation product. Absence of Grx5 causes: 1) iron accumulation in the cell, which in turn could promote oxidative damage, and 2) inactivation of enzymes requiring iron/sulfur clusters for their activity. Reduction of iron levels in grx5 null mutants does not restore the activity of iron/sulfur enzymes, and cell growth defects are not suppressed in anaerobiosis or in the presence of disulfide reductants. Hence, Grx5 forms part of the mitochondrial machinery involved in the synthesis and assembly of iron/sulfur centers.

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Secondary sexual characters often signal qualities such as physiological processes associated with resistance to various sources of stress. When the expression of an ornament is not sex-limited, we can identify the costs and benefits of displaying a trait that is typical of its own sex or of the other sex. Indeed, the magnitude and sign of the covariation between physiology and the extent to which an ornament is expressed could differ between males and females if, for instance, the regulation of physiological processes is sensitive to sex hormones. Using data collected over 14 years in the nocturnal barn owl Tyto alba, we investigated how nestling body mass covaries with a heritable melanin-based sex-trait, females displaying on average larger black feather spots than males. Independently of nestling sex, year and time of the day large-spotted nestlings were heavier than small-spotted nestlings. In contrast, the magnitude and sign of the covariation between nestling body mass and the size of parental spots varied along the day in a way that depended on the year and parental gender. In poor years, offspring of smaller-spotted mothers were heavier throughout the resting period; in the morning, offspring sired by larger-spotted fathers were heavier than offspring of smaller-spotted fathers, while in the evening the opposite pattern was found. Thus, maternal and paternal coloration is differentially associated with behaviour or physiology, processes that are sensitive to time of the day and environmental factors. Interestingly, the covariation between offspring body mass and paternal coloration is more sensitive to these environmental factors than the covariation with maternal coloration. This indicates that the benefit of pairing with differently spotted males may depend on environmental conditions, which could help maintain genetic variation in the face of intense directional (sexual) selection.

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An accumulation of years brings with it an accumulation of experiences. The revision of such experiences usually becomes more recurrent after retirement, a transition time from one period of life to another and, as such, a time in which we, human beings, have a tendency to take stock of our lives. This is actually one of the main issues present in Julian Barnes's last novel The Sense of an Ending (2011). When the main protagonist, a retired man quite comfortable and contented with his present life, receives an unexpected inheritance from the mother of a girlfriend from his university years, he is forced to track down a part of his life that he had left at the back of his mind a long time ago. As he explains his story, the protagonist and narrator of the novel raises a number of questions related to the quality and function of memory as one gets into old age. He experiments the unreliability of memory and questions to what extent memory is constructed through the remembered emotions that invaded him over that episode of his life rather than through the events as they actually took place. On the other hand, the act of revisiting and revising that specific episode, brings with it feelings of guilt and remorse as the protagonist realises that his past acts were not as noble as he remembered them to be. However, these acts are part of the past and they cannot be changed; thus, another question that the novel raises is how to account for those actions of which one does not feel proud and, more importantly, how to manage those bad memories as one gets older.

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Grx3 and Grx4, two monothiol glutaredoxins of Saccharomyces cerevisiae, regulate Aft1 nuclear localisation. We provide evidence of a negative regulation of Aft1 activity by Grx3 and Grx4. The Grx domain of both proteins played an important role in Aft1 translocation to the cytoplasm. This function was not, however, dependent on the availability of iron. Here we demonstrate that Grx3, Grx4 and Aft1 interact each other both in vivo and in vitro, which suggests the existence of a functional protein complex. Interestingly, each interaction occurred independently on the third member of the complex. The absence of both Grx3 and Grx4 induced a clear enrichment of G1 cells in asynchronous cultures, a slow growth phenotype, the accumulation of intracellular iron and a constitutive activation of the genes regulated by Aft1. The grx3grx4 double mutant was highly sensitive to the oxidising agents hydrogen peroxide and t-butylhydroperoxide but not to diamide. The phenotypes of the double mutant grx3grx4 characterised in this study were mainly mediated by the Aft1 function, suggesting that grx3grx4 could be a suitable cellular model for studying endogenous oxidative stress induced by deregulation of the iron homeostasis. However, our results also suggest that Grx3 and Grx4 might play additional roles in the oxidative stress response through proteins other than Aft1.

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To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

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A network of twenty stakes was set up on Johnsons Glacier in order to determine its dynamics. During the austral summers from 1994-95 to 1997-98, we estimated surface velocities, mass balances and ice thickness variations. Horizontal velocity increased dow nstream from 1 m a- 1 near the ice divides to 40 m a- 1 near the ice terminus. The accumulation zone showed low accumulation rates (maximum of 0,6 m a- 1 (ice)), whereas in the lower part of the glacier, ablation rates were 4,3 m a- 1 (ice). Over the 3-year study period, both in the accumulation and ablation zones, we detected a reduction in the ice surface level ranging from 2 to 10 m from the annual ve rt ical velocities and ice-thinning data, the mass balance was obtained and compared with the mass balance field values, resulting in similar estimates. Flux values were calculated using cross-section data and horizontal velocities, and compared with the results obtained by means of mass balance and ice thinning data using the continuity equation. The two methods gave similar results.

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Home enteral nutrition (HEN) is a type of enteral nutrition (EN) which is becoming progressively more widespread in pediatrics due to the benefits it affords to patients, their families and to reducing hospital costs. However, the true extent of its use is unknown in Spain as the data-base set up for this purpose is still underused (Registro de Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria -NEPAD-). More thorough registration of patients in the NEPAD online register will provide information about the characteristics of HEN in Spain: prevalence, diagnosis, the population sector being administered HEN, complications and developments. Likewise, forecast and planning of the necessary resources could be made while those in use could be analysed.

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Tämä tutkimus oli osa sähköistä liiketoimintaa ja langattomia sovelluksia tutkivaa projektia ja tutkimuksen tavoitteena oli selvittää ennustamisen rooli päätöksenteko- ja suunnitteluprosessissa ja määrittää parhaiten soveltuvat ja useimmin käytetyt teknologian ennustusmenetelmät. Ennustusmenetelmiä tarkasteltiin erityisesti uuden teknologian ja pitkän aikavälin ennustamisen näkökulmasta. Tutkimus perustui teknologista ennustamista, pitkän aikavälin suunnittelua ja innovaatioprosesseja käsittelevän kirjallisuuden analysointiin. Materiaalin perusteella kuvataan teknologian ennustamista informaation hankkimisvälineenä organisaatioiden suunnitteluprosessin apuna. Työssä arvioidaan myös seuraavat teknologisen ennustamisen menetelmät: trendianalyysi-, Delfoi-, cross-impact analyysi-, morfologinen analyysi- ja skenaario analyysimenetelmä. Työ tuo esille jokaisen ennustusmenetelmä ominaispiirteet, rajoitukset ja sovellusmahdollisuudet. Käyttäen esiteltyjä menetelmiä, saadaan kerättyä hyödyllistä informaatiota tulevaisuuden näkymistä, joita sitten voidaan käyttää hyväksi organisaatioiden suunnitteluprosesseissa.

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A number of neurotoxic chemicals induce accumulation of neurofilaments in axonal swellings that appear at varying distances from the cell body. This pathology is associated with axonal degeneration of different degrees. The clinical manifestation is most commonly that of a mixed motor-sensory peripheral axonopathy with a disto-proximal pattern of progression, as in cases of chronic exposure to n-hexane and carbon disulphide. It has been demonstrated that protein adduct formation is a primary molecular mechanism of toxicity in these axonopathies, but how this mechanism leads to neurofilament accumulation and axonal degeneration remains unclear. Furthermore, little is known regarding the mechanisms of neurofilamentous axonopathy caused by 3,3′-iminodipropionitrile, an experimental toxin that induces proximal axon swelling that is strikingly similar to that found in early amyotrophic lateral sclerosis. Here, we review the available data and main hypotheses regarding the toxic axonopathies and compare them with the current knowledge of the biological basis of neurofilament transport. We also review recent studies addressing the question of how these axonopathies may cause axonal degeneration. Understanding the mechanisms underlying the toxic axonopathies may provide insight into the relationship between neurofilament behaviour and axonal degeneration, hopefully enabling the identification of new targets for therapeutic intervention. Because neurofilament abnormalities are a common feature of many neurodegenerative diseases, advances in this area may have a wider impact beyond toxicological significance

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Objective. To carry out a pharmacoeconomic analysis of Cyclamen europaeum (CE) in the management of acute rhinosinusitis (ARS) in Spain using data from the PROSINUS study. Study Design. This was a prospective observational study to compare the effectiveness and cost-effectiveness between therapies including CE vs. other therapies in the management of ARS. Methods. The study was carried out as a secondary analysis of the PROSINUS, combining healthcare resource use, productivity loses, and health outcomes from the observational study with costs representative of the Spanish Health System. Results. CE given as monotherapy appears to be more effective (cure rate) than other monotherapies (15.3% higher, p<0.05) and combination (10.3% higher, p<0.05) therapies. The addition of CE to other single-drug or combination therapies showed a statistically significant improvement in terms of cure rates when adding CE to 2-drug combinations (93.9% vs. 76.5%; p<0.05), and no significant effect when added to combinations of three or more drugs (81.1% vs. 79.8; NS). CE based therapies generally showed lower indirect costs, although only the comparison of CE alone vs. other monotherapies, with a net cost savings of 101 per patient, reached statistical significance (331 vs. 432 , p<0.05). In addition, CE-based therapies show lower cost per cured patient in all comparisons except when CE was used in combination with three or more other drugs. Conclusions. The use of Cyclamen europaeum may be associated to better clinical outcomes at no additional cost for the healthcare system, respect to treatments commonly used for ARS in clinical practice.

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Työn tavoitteena on luoda yleinen informaatioinfrastruktuuri autoteollisuuden valmistuskustannusten arviointiin. Nykyään tämä kustannusarviointi on laajassa käytössä oleva menetelmä. Se mahdollistaa tuotekustannusten hallitsemisen, mikä lisää autovalmistajien kilpailukykyä. Kustannusarvioinnissa tarvitaan laadukasta tietoa, mutta suoritetussa tutkimuksessa paljastui, että useat seikat haittaavat tätä arviointia. Erityisesti resurssien vähyys, tiedonhankinta ja tiedon luotettavuuden varmentaminen aiheuttavat ongelmia. Nämä seikat ovat johtaneet kokemusperäisen asiantuntemuksen laajaan käyttöön, minkä johdosta erityisesti kokemattomilla kustannusarvioijilla on vaikeuksia ymmärtää kustannusarvioiden tietovaatimuksia. Tämän johdosta tutkimus tuo esiin kokeneiden kustannusarvioijien käyttämiä tietoja ja tietolähteitä päämääränä lisätä kustannusarvioiden ymmärtämistä. Informaatioinfrastruktuuri, joka sisältää tarvittavan tiedon järkevien ja luotettavien kustannusarvioiden luontiin, perustuu tutkimuksen tuloksiin. Infrastruktuuri määrittelee tarvittavan kustannustiedon ja niiden mahdolliset tietolähteet. Lisäksi se selvittää miksi tieto on tarpeellista ja miten tiedon oikeellisuus pitäisi varmentaa. Infrastruktuuria käytetään yhdessä yleisen kustannusarvioprosessimallin kanssa. Tämä integrointi johtaa tarkempiin ja selkeämpiin kustannusarvioihin autoteollisuudessa.

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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.