Predictors of the Indefinite-Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment. Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Outsourcing and Subcontracting Strategy Creation in a Global Manufacturing Company

Työn tavoitteena oli tutkia lähestymistapoja ostaa-valmistaa - päätöksentekotilanteessa. Näillä päätöksillä voi olla lopputulemana joko oma valmistus tai ulkopuolisen toimittajan käyttäminen, jolloin puhutaanjoko ulkoistetusta tai alihankitusta valmistuksesta. Päätökseen vaikuttavista tekijöistä merkittävimmät on koottu viitekehykseen, joka opastaa huomioimaan eri tekijät, jotka toistuvat olosuhteista riippumatta. . Toimittajakentän mahdollisuuksilla on vaikutusta päätöksentekotilanteessa. Olennainen osa ulkoistamis- ja alihankintastrategiaa liittyy toimittajavalintaan, sekä valittavaan yhteistyömalliin.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Forecasting coal resources and reserves in heterogeneous coal zones using 3D facies models (As Pontes Basin, NW Spain)

Forecasting coal resources and reserves is critical for coal mine development. Thickness maps are commonly used for assessing coal resources and reserves; however they are limited for capturing coal splitting effects in thick and heterogeneous coal zones. As an alternative, three-dimensional geostatistical methods are used to populate facies distributionwithin a densely drilled heterogeneous coal zone in the As Pontes Basin (NWSpain). Coal distribution in this zone is mainly characterized by coal-dominated areas in the central parts of the basin interfingering with terrigenous-dominated alluvial fan zones at the margins. The three-dimensional models obtained are applied to forecast coal resources and reserves. Predictions using subsets of the entire dataset are also generated to understand the performance of methods under limited data constraints. Three-dimensional facies interpolation methods tend to overestimate coal resources and reserves due to interpolation smoothing. Facies simulation methods yield similar resource predictions than conventional thickness map approximations. Reserves predicted by facies simulation methods are mainly influenced by: a) the specific coal proportion threshold used to determine if a block can be recovered or not, and b) the capability of the modelling strategy to reproduce areal trends in coal proportions and splitting between coal-dominated and terrigenousdominated areas of the basin. Reserves predictions differ between the simulation methods, even with dense conditioning datasets. Simulation methods can be ranked according to the correlation of their outputs with predictions from the directly interpolated coal proportion maps: a) with low-density datasets sequential indicator simulation with trends yields the best correlation, b) with high-density datasets sequential indicator simulation with post-processing yields the best correlation, because the areal trends are provided implicitly by the dense conditioning data.

Targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses.

A crucial step in the arenavirus life cycle is the biosynthesis of the viral envelope glycoprotein (GP) responsible for virus attachment and entry. Processing of the GP precursor (GPC) by the cellular proprotein convertase site 1 protease (S1P), also known as subtilisin-kexin-isozyme 1 (SKI-1), is crucial for cell-to-cell propagation of infection and production of infectious virus. Here, we sought to evaluate arenavirus GPC processing by S1P as a target for antiviral therapy using a recently developed peptide-based S1P inhibitor, decanoyl (dec)-RRLL-chloromethylketone (CMK), and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). To control for off-target effects of dec-RRLL-CMK, we employed arenavirus reverse genetics to introduce a furin recognition site into the GPC of LCMV. The rescued mutant virus grew to normal titers, and the processing of its GPC critically depended on cellular furin, but not S1P. Treatment with the S1P inhibitor dec-RRLL-CMK resulted in specific blocking of viral spread and virus production of LCMV. Combination of the protease inhibitor with ribavirin, currently used clinically for treatment of human arenavirus infections, resulted in additive drug effects. In cells deficient in S1P, the furin-dependent LCMV variant established persistent infection, whereas wild-type LCMV underwent extinction without the emergence of S1P-independent escape variants. Together, the potent antiviral activity of an inhibitor of S1P-dependent GPC cleavage, the additive antiviral effect with ribavirin, and the low probability of emergence of S1P-independent viral escape variants make S1P-mediated GPC processing by peptide-derived inhibitors a promising strategy for the development of novel antiarenaviral drugs.

Customization, transparency and proximity: a user- centered content strategy applied to the design of a virtual library website

We present a case study of the redesign of the organizational presentation and content of the Virtual Library website at the Universitat Oberta de Catalunya (Open University of Catalonia, UOC), based on a user-centered design strategy. The aim of the redesign was to provide users with more intuitive, usable and understandable content (textual content, resources and services) by implementing criteria of customization, transparency and proximity. The study also presents a selection of best practices for applying these criteria to the design of other library websites.

The Role of an Enterprise Portal in Knowledge Management Strategy, Case: Private Equity Investor

Työ tutkii yritysportaalin roolia organisaation tietojohtamisessa. Tutkimusongelman ratkaisemiseksi luodaan viitekehys, jossa yritysportaalin ja tietojohtamisen teoriat linkittyvät. Työn empiirisessä osassa viitekehys on pohjana case-yritykselle rakennettavalle yritysportaalille. Laadullinen tutkimus käsittää teoriaosuuden sekä osallistuvaan case-tutkimukseen perustuvan empiriaosuuden. Työn runko muodostuu kahden vastakkaisen tietojohtamisajattelun vuoropuhelusta, jotka ovat informaatioteknologiaan- ja strategiseen johtamiseen perustuvat näkökulmat. Toimivan tietojohtamismallin täytyy sisältää molemmat aspektit. Jokainen organisaatio tarvitsee informaation hallintaan liittyviä toiminnallisuuksia ja täten eksplisiittisen tiedon hallinta tietojärjestelmien avulla on onnistuneen tietojohtamisen kulmakiviä. Tätä perusinfrastruktuuria on mahdollista laajentaa hiljaisen tiedon hallintaan perustuvilla tietojohtamismenetelmillä. Työn ratkaisu näiden kahden näkemyksen, 'kovan' informaatioteknogiaan painottuvan sekä 'pehmeän' ihmisnäkökulman integrointiin, on yritysportaali. Työssä käytettävä yritysportaalin viitekehys rakentuu kolmeen päätoiminnallisuuteen; sisällönhallintaan, yhteistyöominaisuuksiin ja liiketoimintatiedon hallintaan. Työ todistaa yhteyden viitekehyksen sekä tietojohtamisen perusmallien, kuten tietojohtamisen prosessimallin sekä tietoympäristöjen välillä. Yritysportaali voi täten toimia, ei ainoastaan yksittäisten tietojohtamistyökalujen implementoinnissa, vaan tietojohtamisstrategian luomisen apuna tarjoten alustan tai 'katalyytin' kokonaisvaltaiselle tietojohtamiselle.

Customization, transparency and proximity: a user- centered content strategy applied to the design of a virtual library website

We present a case study of the redesign of the organizational presentation and content of the Virtual Library website at the Universitat Oberta de Catalunya (Open University of Catalonia, UOC), based on a user-centered design strategy. The aim of the redesign was to provide users with more intuitive, usable and understandable content (textual content, resources and services) by implementing criteria of customization, transparency and proximity. The study also presents a selection of best practices for applying these criteria to the design of other library websites.

Acute ischemic cerebrovascular events on antiplatelet therapy: what is the optimal prevention strategy?

Even though patients who develop ischemic stroke despite taking antiplatelet drugs represent a considerable proportion of stroke hospital admissions, there is a paucity of data from investigational studies regarding the most suitable therapeutic intervention. There have been no clinical trials to test whether increasing the dose or switching antiplatelet agents reduces the risk for subsequent events. Certain issues have to be considered in patients managed for a first or recurrent stroke while receiving antiplatelet agents. Therapeutic failure may be due to either poor adherence to treatment, associated co-morbid conditions and diminished antiplatelet effects (resistance to treatment). A diagnostic work up is warranted to identify the etiology and underlying mechanism of stroke, thereby guiding further management. Risk factors (including hypertension, dyslipidemia and diabetes) should be treated according to current guidelines. Aspirin or aspirin plus clopidogrel may be used in the acute and early phase of ischemic stroke, whereas in the long-term, antiplatelet treatment should be continued with aspirin, aspirin/extended release dipyridamole or clopidogrel monotherapy taking into account tolerance, safety, adherence and cost issues. Secondary measures to educate patients about stroke, the importance of adherence to medication, behavioral modification relating to tobacco use, physical activity, alcohol consumption and diet to control excess weight should also be implemented.

Strategy Implementation Bottlenecks: Identification, Analysis and Removal

This thesis investigates the strategy implementation process of enterprices; a process whichhas lacked the academic attentioon compared with a rich strategy formation research trdition. Strategy implementation is viewed as a process ensuring tha the strtegies of an organisation are realised fully and quickly, yet with constant consideration of changing circumstances. The aim of this sudy is to provide a framework for identifying, analysing and removing the strategy implementation bottleneck af an organization and thus for intesifying its strategy process.The study is opened by specifying the concept, tasks and key actors of strategy implementation process; especially arguments for the critical implementation role of the top management are provided. In order to facilitate the analysis nad synthetisation of the core findings of scattered doctrine, six characteristic approaches to strategy implementation phenomenon are identified and compared. The Bottleneck Framework is introduced as an instrument for arranging potential strategy realisation problems, prioritising an organisation's implementation obstacles and focusing the improvement measures accordingly. The SUCCESS Framework is introduced as a mnemonic of the seven critical factors to be taken into account when promoting sttrategy implementation. Both frameworks are empirically tested by applying them to real strategy implementation intesification process in an international, industrial, group-structured case enterprise.