Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial.

BACKGROUND: Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt-chromium drug-eluting stent with silicon carbide-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bülach, Switzerland) with the durable polymer-based Xience Prime/Xpedition everolimus-eluting stent (EES) (Xience Prime/Xpedition stent, Abbott Vascular, IL) in an all-comers patient population. DESIGN: The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer sirolimus-eluting stents (SES) or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least 1 lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary end point target lesion failure (TLF) is a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for noninferiority, inclusion of 2,060 patients would provide more than 80% power to detect noninferiority of the biodegradable polymer SES compared with the durable polymer EES at a 1-sided type I error of 0.05. Clinical follow-up will be continued through 5 years. CONCLUSION: The BIOSCIENCE trial will determine whether the biodegradable polymer SES is noninferior to the durable polymer EES with respect to TLF.

The Determinants of Exit in Argentina: Core and Peripheral Regions

This paper analyses the regional determinants of exit in Argentina. We find evidence of a dynamic revolving door by which past entrants increase current exits, particularly in the peripheral regions. In the central regions, current and past incumbents cause an analogous displacement effect. Also, exit shows a U-shaped relationship with respect to the informal economy, although the positive effect is weaker in the central regions. These findings point to the existence of a core-periphery structure in the spatial distribution of exits. Key words: firm exit, count data models, Argentina JEL: R12; R30; C33

Anti-angiogenic therapies in cancer: achievements and open questions.

The approval in 2004 of bevacizumab (Avastin), a neutralizing monoclonal antibody directed against vascular endothelial growth factor (VEGF) as the first anti-angiogenic systemic drug to treat cancer patients validated the notion introduced 33 years earlier by Dr. Judah Folkman, that inhibition of tumor angiogenesis might be a valid approach to control tumor growth. Anti-angiogenic therapy was greeted in the clinic a major step forward in cancer treatment. At the same time this success recently boosted the field to the quest for new anti-angiogenic targets and drugs. In spite of this success, however, some old questions in the field have remained unanswered and new ones have emerged. They include the identification for surrogate markers of angiogenesis and anti-angiogenesis, the understanding about how anti-angiogenic therapy and chemotherapy synergize, the characterization of the biological consequences of sustained suppression of angiogenesis on tumor biology and normal tissue homeostasis, and the mechanisms of tumor escape from anti-angiogenesis. In this review we summarize some of these outstanding questions, and highlight future challenges in clinical, translational and experimental research in anti-angiogenic therapy that need to be addressed in order to improve current treatments and to design new drugs.

The role of integrins in glioma biology and anti-glioma therapies.

The tumor environment is critical for tumor maintenance and progression. Integrins are a large family of cell surface receptors mediating the interaction of tumor cells with their microenvironment and play important roles in glioma biology, including migration, invasion, angiogenesis and tumor stem cell anchorage. Here, we review preclinical and clinical data on integrin inhibition in malignant gliomas. Various pharmacological approaches to the modulation of integrin signaling have been explored including antibodies and peptide-based agents. Cilengitide, a cyclic RGD-mimetic peptide of αvβ3 and αvβ5 integrins is in advanced clinical development in glioblastoma. Cilengitide had only limited activity as a single agent in glioblastoma, but, when added to standard radiochemotherapy, appeared to prolong progression-free and overall survival in patients with newly diagnosed glioblastomas and methylation of the promoter of the O⁶ methylguanine methyltransferase (MGMT) gene. MGMT gene promoter methylation in turn predicts benefit from alkylating chemotherapy. A phase III randomized clinical trial in conjunction with standard radiochemotherapy in newly diagnosed glioblastoma patients with MGMT gene promoter methylation has recently completed accrual (EORTC 26071-22072). A companion trial explores a dose-escalated regimen of cilengitide added to radiotherapy plus temozolomide in patients without MGMT gene promoter methylation. Promising results in these trials would probably result in a broader interest in integrins as targets for glioma therapy and hopefully the development of a broader panel of anti-integrin agents.

Needs assessment and design of the intervention for high risk sex offenders social reintegration

Executive report of the adaptation study "Needs assessment and design of the intervention for high risk sex offenders social reintegration: Adaptation of the Circles of Support and Accountability to the Penal Enforcement System of Catalonia".

Population genetic structure in the native and introduced range of the Argentine ant/

SUMMARY : The evolution of animal societies, where some individuals forego their own reproductive opportunities to help others to reproduce, poses an evolutionary paradox that can be traced back to Darwin. Altruism may evolve through kin selection when the donor and recipient of altruistic acts are related to each other. In social insects, workers are generally highly related to the brood they rear when colonies are headed by a single queen. Yet some ants have an extraordinary social organization, called unicoloniality, whereby individuals from separate nests mix freely to form large supercolonies, which in some cases extend over hundreds of km. These supercolonies are characterised by a high number of queens (polygyny) and an absence of clear colony boundaries. This type of social organization represents an evolutionary paradox because relatedness between nestmates is effectively zero. In such conditions, kin selection cannot account for the evolution of reproductive altruism. Moreover, unicoloniality is thought to be unstable over time, because workers that can no longer aid close relatives may evolve more selfish strategies. The Argentine ant (Linepithema humile) is a highly invasive species listed among the hundred world's worst invaders by the UICN. Native from South America, L. humile has been accidentally introduced throughout the world. Native populations have been described as noninvasive with a family-based organization. In contrast, within its introduction range, they form unicolonial supercolonies that contain numerous nests without intraspecific aggression. The development of such unicolonial populations has been explained as a direct consequence of the ant's introduction into a new habitat, favouring a transition from family-based to open colonies. To determine if the social structure of the Argentine ant is fundamentally different between the native and the introduced range, we studied genetically and behaviourally native and introduced populations of L. humile over different geographic scales. Our results clearly indicated that there are no fundamental differences in the social organisation of the Argentine ant between the two ranges. Our investigations revealed that, contrary to previous claims, native populations have a unicolonial social organisation very similar to that observed in the introduced range. Consequently, the unicolonial social structure of the Argentine ant does not stem from a shift in social organization associated with introduction into new habitats but evolved in the native range and is likely a stable, evolutionarily ancient adaptation to the local environment. Our study on native populations of L. humile also gave important insight in the comprehension of the evolution of unicoloniality in the Argentine ant. Native supercolonies are relatively small compared to introduced ones and may co-habit in a same population. These supercolonies are genetically highly differentiated leading to a significant relatedness among nestmate workers when the different supercolonies of a population are taken as a reference population. This provides the necessary conditions for loin selection to operate. Furthermore, we examined a native population over time, which revealed a high supercolony extinction rate. If more competitive supercolonies are more likely to survive or replace other supercolonies, a subtle dynamical process between the spread of selfish traits within supercolony and the selective elimination of supercolonies with such traits may allow a stable equilibrium and the persistence of unicoloniality over time. Finally, a worldwide study of the Argentine ant showed that the introduced supercolonies originate from numerous independent introduction events. In conclusion, the success of the Argentine ant does not stem from a shift in social organization associated with its introduction into new habitats, but is most probably explained by the intrinsic characteristics developed in its native range. RESUME : L'altruisme de reproduction où certains individus renoncent à leur propre reproduction pour aider d'autres individus à se reproduire constitue l'un des plus grand paradoxe de l'évolution. En effet, comment expliquer l'évolution de comportements qui tendent à augmenter les chances de survie et le succès reproductif d'autres individus, alors que ces actes diminuent l'aptitude de leurs auteurs ? La théorie de la sélection de parentèle permet de résoudre ce problème. Cette théorie stipule qu'en aidant de proches parents à se reproduire, les individus peuvent promouvoir indirectement la transmission de copies de leurs propres gènes à la génération suivante. Chez les insectes sociaux, l'altruisme des ouvrières s'explique par la théorie de sélection de parentèle lorsque les colonies sont monogynes (constituées d'une seule reine) puisque les ouvrières sont fortement apparentées aux couvains dont elles s'occupent. Par contre, les espèces dites unicoloniales, dont les colonies forment des réseaux de nids appelés supercolonies, représentent toujours un paradoxe pour les théories de l'évolution puisque l'apparentement entre les différents individus d'un nid est nulle. De plus, l'unicolonialité ne devrait pas être stable sur le long terme parce que les ouvrières qui ne s'occupent plus de leur apparentés devraient développer des stratégies plus égoïstes au cours du temps. La fourmi d'Argentine (Linepithema humile) est une espèce invasive ayant un impact considérable sur son environnement. Originaire d'Amérique du Sud, elle a été introduite dans pratiquement toutes les régions du monde dont le climat est de type méditerranéen. Son incroyable succès invasif s'explique par sa structure sociale unicoloniale observée dans chacun des pays où elle a été introduite. Par contre, les rares études effectuées en Argentine ont suggéré que la fourmi d'Argentine n'était pas unicoloniale dans son aire native. L'unicolonialité chez la fourmi d'Argentine était donc considéré comme une conséquence de son introduction dans de nouveaux environnements. Durant cette thèse, nous avons vérifié si la structure sociale de cette espèce différait fondamentalement entre l'aire native et introduite. Pour cela, nous avons étudié, à différentes échelles géographiques, des populations introduites et argentines avec une approche génétique et comportementale. L'ensemble de nos résultats montrent que les différences entre les deux structure sociales ne sont pas aussi importantes que ce que l'on imaginait. Les populations natives sont aussi constituées de réseaux de nids coopérants. La taille de ses supercolonies est toutefois bien moins importante en Argentine et il n'est pas rare de trouver plusieurs supercolonies cohabitantes dans une même population. Nous avons démontré que ces réseaux de nids étaient constitués d'individus qui sont plus apparentés entre eux qu'ils ne le sont avec les individus d'autres supercolonies, ainsi l'unicolonialité dans son aire d'origine ne représente pas un réel paradoxe pour les théories de l'évolution. Finalement nous avons étudié la même population en Argentine à six ans d'intervalle et avons constaté que les supercolonies avaient un taux de survie très faible ce qui pourrait expliquer la stabilité de l'unicolonialité au cours du temps. Si les supercolonies les plus compétitives survivent mieux que les supercolonies dans lesquelles apparaissent des traits égoïstes, on devrait alors observer une dynamique entre l'apparition de traits égoïstes et l'élimination des supercolonies dans lesquelles ces traits égoïstes évolueraient. Finalement, une étude mondiale nous a montré que les supercolonies étaient originaires de nombreux événements d'introductions indépendants. En conclusion, le succès invasif de la fourmi d'Argentine n'est donc pas dû à un changement de comportement associé à son introduction mais est lié aux caractéristiques qu'elle a développées en Argentine.

Emotion expression in body action and posture

Emotion communication research strongly focuses on the face and voice as expressive modalities, leaving the rest of the body relatively understudied. Contrary to the early assumption that body movement only indicates emotional intensity, recent studies show that body movement and posture also convey emotion specific information. However, a deeper understanding of the underlying mechanisms is hampered by a lack of production studies informed by a theoretical framework. In this research we adopted the Body Action and Posture (BAP) coding system to examine the types and patterns of body movement that are employed by 10 professional actors to portray a set of 12 emotions. We investigated to what extent these expression patterns support explicit or implicit predictions from basic emotion theory, bi-dimensional theory, and componential appraisal theory. The overall results showed partial support for the different theoretical approaches. They revealed that several patterns of body movement systematically occur in portrayals of specific emotions, allowing emotion differentiation. While a few emotions were prototypically encoded by one particular pattern, most emotions were variably expressed by multiple patterns, many of which can be explained as reflecting functional components of emotion such as modes of appraisal and action readiness. It is concluded that further work in this largely underdeveloped area should be guided by an appropriate theoretical framework to allow a more systematic design of experiments and clear hypothesis testing.

Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients.

BACKGROUND: Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited. STUDY DESIGN/METHODS: Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients' and their families' quality of life was assessed. RESULTS: The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents' point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls. CONCLUSION: Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.

Permanent magnet synchronous motor for industrial inverter applications - analysis and design

During the latest few years the need for new motor types has grown, since both high efficiency and an accurate dynamic performance are demanded in industrial applications. For this reason, new effective control systems such as direct torque control (DTC) have been developed. Permanent magnet synchronous motors (PMSM) are well suitable for new adjustable speed AC inverter drives, because their efficiency and power factor are not depending on the pole pair number and speed to the same extent as it is the case in induction motors. Therefore, an induction motor (IM) with a mechanical gearbox can often be replaced with a direct PM motor drive. Space as well as costs will be saved, because the efficiency increases and the cost of maintenance decreases as well. This thesis deals with design criterion, analytical calculation and analysis of the permanent magnet synchronous motor for both sinusoidal air-gap flux density and rectangular air-gapflux density. It is examined how the air-gap flux, flux densities, inductances and torque can be estimated analytically for salient pole and non-salient pole motors. It has been sought by means of analytical calculations for the ultimate construction for machines rotating at relative low 300 rpm to 600 rpm speeds, which are suitable speeds e.g. in Pulp&Paper industry. The calculations are verified by using Finite Element calculations and by measuring of prototype motor. The prototype motor is a 45 kW, 600 rpm PMSM with buried V-magnets, which is a very appropriate construction for high torque motors with a high performance. With the purposebuilt prototype machine it is possible not only to verify the analytical calculations but also to show whether the 600 rpm PMSM can replace the 1500 rpm IM with a gear. It can also be tested if the outer dimensions of the PMSM may be the same as for the IM and if the PMSM in this case can produce a 2.5 fold torque, in consequence of which it may be possible to achieve the same power. The thesis also considers the question how to design a permanent magnet synchronous motor for relatively low speed applications that require a high motor torqueand efficiency as well as bearable costs of permanent magnet materials. It is shown how a selection of different parameters affects the motor properties. Key words: Permanent magnet synchronous motor, PMSM, surface magnets, buried magnets

Mobile Communications within the European Union: The Role of Location in the Evolution and Forecasting of the Diffusion Process

In the European Union, the importance of mobile communications was realized early on. The process of mobile communications becoming ubiquitous has taken time, as the innovation of mobile communications diffused into the society. The aim of this study is to find out how the evolution and spatial patterns of the diffusion of mobile communications within the European Union could be taken into account in forecasting the diffusion process. There is relatively lot of research of innovation diffusion on the individual (micro) andthe country (macro) level, if compared to the territorial level. Territorial orspatial diffusion refers either to the intra-country or inter-country diffusionof an innovation. In both settings, the dif- fusion of a technological innovation has gained scarce attention. This study adds knowledge of the diffusion between countries, focusing especially on the role of location in this process. The main findings of the study are the following: The penetration rates of the European Union member countries have become more even in the period of observation, from the year 1981 to 2000. The common digital GSM system seems to have hastened this process. As to the role of location in the diffusion process, neighboring countries have had similar diffusion processes. They can be grouped into three, the Nordic countries, the central and southern European countries, and the remote southern European countries. The neighborhood effect is also domi- nating in thegravity model which is used for modeling the adoption timing of the countries. The subsequent diffusion within a country, measured by the logistic model in Finland, is af- fected positively by its economic situation, and it seems to level off at some 92 %. Considering the launch of future mobile communications systemsusing a common standard should implicate an equal development between the countries. The launching time should be carefully selected as the diffusion is probably delayed in economic downturns. The location of a country, measured by distance, can be used in forecasting the adoption and diffusion. Fi- nally, the result of penetration rates becoming more even implies that in a relatively homoge- nous set of countries, such as the European Union member countries, the estimated final pene- tration of a single country can be used for approximating the penetration of the others. The estimated eventual penetration of Finland, some 92 %, should thus also be the eventual level for all the European Union countries and for the European Union as a whole.

Patents in the Information and Communications Technology Sector - Development Trends, Problem Areas and Pressures for Change

The patent system was created for the purpose of promoting innovation by granting the inventors a legally defined right to exclude others in return for public disclosure. Today, patents are being applied and granted in greater numbers than ever, particularly in new areas such as biotechnology and information andcommunications technology (ICT), in which research and development (R&D) investments are also high. At the same time, the patent system has been heavily criticized. It has been claimed that it discourages rather than encourages the introduction of new products and processes, particularly in areas that develop quickly, lack one-product-one-patent correlation, and in which theemergence of patent thickets is characteristic. A further concern, which is particularly acute in the U.S., is the granting of so-called 'bad patents', i.e. patents that do not factually fulfil the patentability criteria. From the perspective of technology-intensive companies, patents could,irrespective of the above, be described as the most significant intellectual property right (IPR), having the potential of being used to protect products and processes from imitation, to limit competitors' freedom-to-operate, to provide such freedom to the company in question, and to exchange ideas with others. In fact, patents define the boundaries of ownership in relation to certain technologies. They may be sold or licensed on their ownor they may be components of all sorts of technology acquisition and licensing arrangements. Moreover, with the possibility of patenting business-method inventions in the U.S., patents are becoming increasingly important for companies basing their businesses on services. The value of patents is dependent on the value of the invention it claims, and how it is commercialized. Thus, most of them are worth very little, and most inventions are not worth patenting: it may be possible to protect them in other ways, and the costs of protection may exceed the benefits. Moreover, instead of making all inventions proprietary and seeking to appropriate as highreturns on investments as possible through patent enforcement, it is sometimes better to allow some of them to be disseminated freely in order to maximize market penetration. In fact, the ideology of openness is well established in the software sector, which has been the breeding ground for the open-source movement, for instance. Furthermore, industries, such as ICT, that benefit from network effects do not shun the idea of setting open standards or opening up their proprietary interfaces to allow everyone todesign products and services that are interoperable with theirs. The problem is that even though patents do not, strictly speaking, prevent access to protected technologies, they have the potential of doing so, and conflicts of interest are not rare. The primary aim of this dissertation is to increase understanding of the dynamics and controversies of the U.S. and European patent systems, with the focus on the ICT sector. The study consists of three parts. The first part introduces the research topic and the overall results of the dissertation. The second part comprises a publication in which academic, political, legal and business developments that concern software and business-method patents are investigated, and contentiousareas are identified. The third part examines the problems with patents and open standards both of which carry significant economic weight inthe ICT sector. Here, the focus is on so-called submarine patents, i.e. patentsthat remain unnoticed during the standardization process and then emerge after the standard has been set. The factors that contribute to the problems are documented and the practical and juridical options for alleviating them are assessed. In total, the dissertation provides a good overview of the challenges and pressures for change the patent system is facing,and of how these challenges are reflected in standard setting.

Phyllochron estimation in intercropped strawberry and monocrop systems in a protected environment

The phyllochron is defined as the time required for the appearance of successive leaves on a plant; this characterises plant growth, development and adaptation to the environment. To check the growth and adaptation in cultivars of strawberry grown intercropped with fig trees, it was estimated the phyllochron in these production systems and in the monocrop. The experiment was conducted in greenhouses at the University of Passo Fundo (28º15'41'' S, 52º24'45'' W and 709 m) from June 8th to September 4th, 2009; this comprised the period of transplant until the 2nd flowering. The cultivars Aromas, Camino Real, Albion, Camarosa and Ventana, which seedlings were originated from the Agrícola LLahuen Nursery in Chile, as well as Festival, Camino Real and Earlibrite, originated from the Viansa S.A. Nursery in Argentina, were grown in white polyethylene bags filled with commercial substrate (Tecnomax®) and evaluated. The treatments were arranged in a randomised block design and four replicates were performed. A linear regression was realized between the leaf number (LN) in the main crown and the accumulated thermal time (ATT). The phyllochron (degree-day leaf-1) was estimated as the inverse of the angular coefficient of the linear regression. The data were submitted to ANOVA, and when significance was observed, the means were compared using the Tukey test (p < 0.05). The mean and standard deviation of phyllochrons of strawberry cultivars intercropped with fig trees varied from 149.35ºC day leaf-1 ± 31.29 in the Albion cultivar to 86.34ºC day leaf-1 ± 34.74 in the Ventana cultivar. Significant differences were observed among cultivars produced in a soilless environment with higher values recorded for Albion (199.96ºC day leaf-1 ± 29.7), which required more degree-days to produce a leaf, while cv. Ventana (85.76ºC day leaf-1 ± 11.51) exhibited a lower phyllochron mean value. Based on these results, Albion requires more degree-days to issue a leaf as compared to cv. Ventana. It was conclude that strawberry cultivars can be grown intercropped with fig trees (cv. Roxo de Valinhos).

Measuring organizational capabilities in the engineering and consulting industry

Tämän työn tarkoituksena oli tutkia kuinka organisaation kyvykkyyksiä voidaan mitata engineering- ja konsultointialalla käyttämällä ns. kyvykkyysauditointimenetelmää. Päämotiivit aineettoman omaisuuden mittaamiseksi tunnistettiin kirjallisuuskatsauksen pohjalta. Erilaisten menetelmien etuja ja haittoja tutkittiin, jotta kyvykkyysauditoinnin suorittamiseen liittyvät haasteet ja vaatimukset tulisivat tunnistetuiksi. Kyvykkyysauditoinnin rakentaminen vaati teollisuudenalan erityispiirteiden tunnistamista. Niiksi havaittiin tietointensiivisyys ja projektikeskeisyys. Auditoinnin implementaatioprosessi koostui neljästä osasta, joista kolmen ensimmäisen suorittamiseen case-yritys antoi merkittävän panoksensa. Kriittisten menestystekijöiden selvittämisen jälkeen voitiin niihin vaikuttavat organisaation kyvykkyydet tunnistaa ja arviointi suorittaa. Arvioinnit kerättiin sisäisiltä ja ulkoisilta arvioijilta, ja ne muodostivat pohjan analyysille, joka selvitti yrityksen kehittämistarpeita. Kyvykkyysauditoinnin hyödyiksi laskettiin kasvanut tietämys yrityksen vahvuuksista ja heikkouksista sekä mahdollisuus tarkkailla säännöllisesti sen kokonaissuorituskykyä ja parantaa sitä.

Tales of the City. Storytelling as a contemporary tool of urban planning and design

Almost thirty years ago, as the social sciences underwent their 'discursive turn', Bernardo Secchi (1984) drew, in what he called the 'urban planning narrative', the attention of planners to the production of myths, turning an activity often seen as primarily technical into one centred around the production of images and ideas. This conception of planning practice gave rise to a powerful current of research in English-speaking countries. Efforts were made to both combine the urban planning narrative with storytelling and to establish storytelling as a prescriptive or descriptive model for planning practice. Thus, just as storytelling is supposed to have led democratic communication off track through a pronounced concern for a good story, storytelling applied to the field of urban production may have led to an increasing preoccupation with staging and showmanship for projects to the detriment of their real inclusion in political debate. It is this possible transformation of the territorial action that will be the focus of the articles collected in this special issue of Articulo - Journal of urban research.