Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway

Either calorie restriction, loss of function of the nutrient-dependent PKA or TOR/SCH9 pathways, or activation of stress defences improves longevity in different eukaryotes. However, the molecular links between glucose depletion, nutrient-dependent pathways and stress responses are unknown. Here we show that either calorie restriction or inactivation of nutrient-dependent pathways induces life-span extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 MAP kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress program, whereas such activation does not occur under glucose-rich conditions. Deletion of the genes coding for the SCH9-homologue Sck2 or the Pka1 kinases, or mutations leading to constitutive activation of the Sty1 stress pathway increase life span under glucose-rich conditions, and importantly such beneficial effects depend ultimately on Sty1. Furthermore, cells lacking Pka1 display enhanced oxygen consumption and Sty1 activation under glucose-rich conditions. We conclude that calorie restriction favours oxidative metabolism, reactive oxygen species production and Sty1 MAP kinase activation, and this stress pathway favours life-span extension.

Discourse, knowledge, power and politics: towards critical epistemic discourse analysis

Although both are fundamental terms in the humanities and social sciences, discourse and knowledge have seldom been explicitly related, and even less so in critical discourse studies. After a brief summary of what we know about these relationships in linguistics, psychology, epistemology and the social sciences, with special emphasis on the role of knowledge in the formation of mental models as a basis for discourse, I examine in more detail how a critical study of discourse and knowledge may be articulated in critical discourse studies. Thus, several areas of critical epistemic discourse analysis are identified, and then applied in a study of Tony Blair’s Iraq speech on March 18, 2003, in which he sought to legitimatize his decision to go to war in Iraq with George Bush. The analysis shows the various modes of how knowledge is managed and manipulated of all levels of discourse of this speech.

BIMS: Biomedical Information Management System

This final year project presents the design principles and prototype implementation of BIMS (Biomedical Information Management System), a flexible software system which provides an infrastructure to manage all information required by biomedical research projects.The BIMS project was initiated with the motivation to solve several limitations in medical data acquisition of some research projects, in which Universitat Pompeu Fabra takes part. These limitations,based on the lack of control mechanisms to constraint information submitted by clinicians, impact on the data quality, decreasing it.BIMS can easily be adapted to manage information of a wide variety of clinical studies, not being limited to a given clinical specialty. The software can manage both, textual information, like clinical data (measurements, demographics, diagnostics, etc ...), as well as several kinds of medical images (magnetic resonance imaging, computed tomography, etc ...). Moreover, BIMS provides a web - based graphical user interface and is designed to be deployed in a distributed andmultiuser environment. It is built on top of open source software products and frameworks.Specifically, BIMS has been used to represent all clinical data being currently used within the CardioLab platform (an ongoing project managed by Universitat Pompeu Fabra), demonstratingthat it is a solid software system, which could fulfill requirements of a real production environment.

Survival and Sensemaking: Organizational Resilience in a Wall Street Trading Room After 9/11

How do organizations cope with extreme uncertainty? The existing literature is divided on this issue: some argue that organizations deal best with uncertainty in the environment by reproducing it in the organization, whereas others contend that the orga nization should be protected from the environment. In this paper we study the case of a Wall Street investment bank that lost its entire office and trading technology in the terrorist attack of September 11 th. The traders survived, but were forced to relocate to a makeshift trading room in New Jersey. During the six months the traders spent outside New York City, they had to deal with fears and insecurities inside the company as well as outside it: anxiety about additional attacks, questions of professional identity, doubts about the future of the firm, and ambiguities about the future re-location of the trading room. The firm overcame these uncertainties by protecting the traders' identities and their ability to engage in sensemaking. The organization held together through a leadership style that managed ambiguities and created the conditions for new solutions to emerge.

Organisational Values as "Attractors of Chaos": An Emerging Cultural Change to Manage Organisational Complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.

Regulatory ambivalence and the limitations of pharmaceutical policy in Spain

Broadly speaking, pharmaceutical policy in Spain has been unable to control either the price or thevolume of drugs prescribed. Limited attempts have been made to bring together the regulation of thepharmaceutical market and policies, in pursuit of the desired goals of efficiency and quality. Thispaper assesses the regulation of the Spanish pharmaceutical market over the last two decades byexamining regulation and policy and the available empirical evidence on their appreciable effects,and presents recommendations for policy design. Our findings suggest that policies aiming to improveefficiency and quality have not managed to contain costs, while cost-effectiveness is still overlooked.We argue that future policies should encourage broader participation in the decision-making processesand promote a higher degree of competition, especially from generic drugs.

Resolving identities: Successive crises in a trading room after 9/11

How do organizations cope with extreme uncertainty? The existing literatureis divided on this issue: some argue that organizations deal best withuncertainty in the environment by reproducing it in the organization, whereasothers contend that the orga nization should be protected from theenvironment. In this paper we study the case of a Wall Street investment bankthat lost its entire office and trading technology in the terrorist attack ofSeptember 11 th. The traders survived, but were forced to relocate to amakeshift trading room in New Jersey. During the six months the traders spentoutside New York City, they had to deal with fears and insecurities insidethe company as well as outside it: anxiety about additional attacks,questions of professional identity, doubts about the future of the firm, andambiguities about the future re-location of the trading room. The firmovercame these uncertainties by protecting the traders identities and theirability to engage in sensemaking. The organization held together through aleadership style that managed ambiguities and created the conditions for newsolutions to emerge.

Financiación capitativa, articulación entre niveles asistenciales y descentralización de las organizaciones sanitarias

Public organisations are subjected to weak incentivesfor competition. Therefore, institutional Darwinismcannot apply. Regulation and performance monitoring isrequired to protect the public interest. This isparticularly the case of organisations in the healthcare arena, since strong incentives may risk the wholesupply of public health services. Regarding to the pathdependence of the Spanish public health institutionswith respect to the international experience and theobserved health technological changes, this paper triesto ground some theoretical bases for the organisationalchange in our health system. We do this by building ourargument from the very basic public goal: the improvementof the health status of the Spanish population. Thisrequires a better integration of health care services.To this regard, capitation in finance shows somecomparative advantages: it takes an integral view forthe care of the population, it allows for a betterdecentralisation ('deconcentration') of risks to healthproviders and favours managed care under a globalperspective, replacing partial payment to differentproviders. However, the paper shows some potentiallimitations for this purpose and the need of a gradualstrategy for its implementation.

Economic growth and investment in the Arab world

This paper analyses the economic growth performance in the Arab world overthe last forty years. The Arab world has managed to reduce povertyperformance despite its relatively disappointing growth performance. Werelate this poor performance of both oil and non-oil producers toinvestment. Contrary to widespread belief, we do not find evidence that lowquantity of investment is the main of low growth. The decline in theinvestment rate followed rather than preceded the reduction in the aggregategrowth rate. We conclude that the low quality of investment projects is thekey determinant of growth. The excessive reliance on public investment, thelow quality of financial institutions, the bad business environment (due topolitical and social instability and to excessive public intervention andoverregulation) and the low quality of human capital are importantdeterminants of systematically unproductive investment decisions and, thus,low economic growth.

Organisational values as "attractors of chaos": An emerging cultural change to manage organisational complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.

The Spanish motor industry in the first third of the 20th Century: A lost opportunity

The Spanish automobile industry had a late start. Although the country proved capable of short production runs of high-quality vehicles during the first third of the century it never managed to build up its own industry, unlike Great Britain, France, or Italy. What then, were the critical shortcomings that prevented the establishment of large Spanish motor manufacturers? Put another way, why did all of the companies set up during the first half-century fail to survive? This paper attempts to shed some light on these questions, employing a wide-ranging analysis of both internal and external factors affecting the industry. A feeble internal market, lack of resources and production factors are usually adduced as reasons, as are Spain's general economic backwardness and the role played by the public authorities. However, this paper mainly focuses on the internal factors concerning company strategy and organisation. A comparison with the Italian case helps put the traditional arguments in proper perspective and highlights those covering business strategies. Finally, we argue that a broad range of factors needs to be analysed to fully understand why Spain failed to establish a motor industry.

Population based resource allocation: The use of hybrid risk adjustment

The emphasis on integrated care implies new incentives that promote coordinationbetween levels of care. Considering a population as a whole, the resource allocation systemhas to adapt to this environment. This research is aimed to design a model that allows formorbidity related prospective and concurrent capitation payment. The model can be applied inpublicly funded health systems and managed competition settings.Methods: We analyze the application of hybrid risk adjustment versus either prospective orconcurrent risk adjustment formulae in the context of funding total health expenditures for thepopulation of an integrated healthcare delivery organization in Catalonia during years 2004 and2005.Results: The hybrid model reimburses integrated care organizations avoiding excessive risktransfer and maximizing incentives for efficiency in the provision. At the same time, it eliminatesincentives for risk selection for a specific set of high risk individuals through the use ofconcurrent reimbursement in order to assure a proper classification of patients.Conclusion: Prospective Risk Adjustment is used to transfer the financial risk to the healthprovider and therefore provide incentives for efficiency. Within the context of a National HealthSystem, such transfer of financial risk is illusory, and the government has to cover the deficits.Hybrid risk adjustment is useful to provide the right combination of incentive for efficiency andappropriate level of risk transfer for integrated care organizations.

Fermat's treatise on quadrature: A new reading

The Treatise on Quadrature of Fermat (c. 1659), besides containing the first known proof of the computation of the area under a higher parabola, R x+m/n dx, or under a higher hyperbola, R x-m/n dx with the appropriate limits of integration in each case , has a second part which was not understood by Fermat s contemporaries. This second part of the Treatise is obscure and difficult to read and even the great Huygens described it as'published with many mistakes and it is so obscure (with proofs redolent of error) that I have been unable to make any sense of it'. Far from the confusion that Huygens attributes to it, in this paper we try to prove that Fermat, in writing the Treatise, had a very clear goal in mind and he managed to attain it by means of a simple and original method. Fermat reduced the quadrature of a great number of algebraic curves to the quadrature of known curves: the higher parabolas and hyperbolas of the first part of the paper. Others, he reduced to the quadrature of the circle. We shall see how the clever use of two procedures, quite novel at the time: the change of variables and a particular case of the formulaof integration by parts, provide Fermat with the necessary tools to square very easily curves as well-known as the folium of Descartes, the cissoid of Diocles or the witch of Agnesi.

Proving the performance of a new revenue management system

Revenue management (RM) is a complicated business process that can best be described ascontrol of sales (using prices, restrictions, or capacity), usually using software as a tool to aiddecisions. RM software can play a mere informative role, supplying analysts with formatted andsummarized data who use it to make control decisions (setting a price or allocating capacity fora price point), or, play a deeper role, automating the decisions process completely, at the otherextreme. The RM models and algorithms in the academic literature by and large concentrateon the latter, completely automated, level of functionality.A firm considering using a new RM model or RM system needs to evaluate its performance.Academic papers justify the performance of their models using simulations, where customerbooking requests are simulated according to some process and model, and the revenue perfor-mance of the algorithm compared to an alternate set of algorithms. Such simulations, whilean accepted part of the academic literature, and indeed providing research insight, often lackcredibility with management. Even methodologically, they are usually awed, as the simula-tions only test \within-model" performance, and say nothing as to the appropriateness of themodel in the first place. Even simulations that test against alternate models or competition arelimited by their inherent necessity on fixing some model as the universe for their testing. Theseproblems are exacerbated with RM models that attempt to model customer purchase behav-ior or competition, as the right models for competitive actions or customer purchases remainsomewhat of a mystery, or at least with no consensus on their validity.How then to validate a model? Putting it another way, we want to show that a particularmodel or algorithm is the cause of a certain improvement to the RM process compared to theexisting process. We take care to emphasize that we want to prove the said model as the causeof performance, and to compare against a (incumbent) process rather than against an alternatemodel.In this paper we describe a \live" testing experiment that we conducted at Iberia Airlineson a set of flights. A set of competing algorithms control a set of flights during adjacentweeks, and their behavior and results are observed over a relatively long period of time (9months). In parallel, a group of control flights were managed using the traditional mix of manualand algorithmic control (incumbent system). Such \sandbox" testing, while common at manylarge internet search and e-commerce companies is relatively rare in the revenue managementarea. Sandbox testing has an undisputable model of customer behavior but the experimentaldesign and analysis of results is less clear. In this paper we describe the philosophy behind theexperiment, the organizational challenges, the design and setup of the experiment, and outlinethe analysis of the results. This paper is a complement to a (more technical) related paper thatdescribes the econometrics and statistical analysis of the results.

Entrepreneurial structure of the mercantile company in pre-industrial Catalonia

The mercantile company was the basic form of enterprise in pre-industrial Catalonia. The aim of this paper is to study the formation and development of the mercantile companies in Barcelona whose end was the wholesale and retail sale of textiles in the botigues de teles (textile retail shops) throughout the eighteenth century. These firms were officially registered before a notary and their deeds reveal how these establishments were administered and managed.The study covers a sample of 121 mercantile companies, and the articles and documentation that were put into effect by 32 notaries who were active in Barcelona in the 18th century have been consulted in their entirety. From an initial selection of documentation, a total of 228 deeds registering companies have been found, 107 of which (47%) relate to the creation of companies whose various activities were centred in taverns, textile manufacturing, braiding.... While the 121 companies, which make up our sample and which account for 53% of the deeds registered with the notaries mentioned above, focused exclusively on the management of textile retail shops located in the commercial heart of the city. Thus one point of interest that the documentation reveals is that the majority of the mercantile companies registered by Barcelona notaries throughout the 18th century were establishments which traded in textiles. The first part of the article focuses on the structural characteristics of these enterprises, the number and socio-professional status of the partners and the extent of each partner s involvement in the administration and management. The second part of the article examines the capital investment made by each partner, their rights and obligations agreed on, the sharing out of profits and possible losses and the duration of the companies. The final aim of the paper is to highlight the evolution of these companies through one specific case.