Primary Prevention and Screening Strategies for Colorectal Cancer: Which Strategy Should Take?

Objective: To explore and define the utility of different strategies for primary prevention (ASA, diet, physical activity) and strategies of screening test (FOBT, sigmoidoscopy, colonoscopy, etc.) for colorectal cancer. Data source: Databases consulted were MEDLINE (1966 to 2006), DARE (1980 to 2006), Cochrane Central Register of Controlled Trials, Cochrane Collaboration’s Registry of Clinical Trials, Cochrane Database of Systematic Reviews and LILACS. Study selection: Studies such clinical trial, cohort and case-control studies of the effectiveness of tests for screening and primary prevention adenoma and colorectal cancer were identified by two reviewers. Data Extraction: The extraction of data and its evaluation is done in most of the process so paired. Limitations: Not strictly complies with the methodology of a systematic review and therefore reproducibility is questionable, the conclusions of this study should be extrapolated with caution. Conclusions: The major strategy of screening on the effectiveness of early detection of premalignant lesions or cancer is colonoscopy every 5 years, however it is necessary to evaluate this measure cost-effectiveness studies. For primary prevention, aspirin and cyclooxygenase-2 inhibitors reduce the incidence of colorectal adenomas. Aspirin can reduce colorectal cancer incidence. However, these medications may be associated with a significant risk of cardiovascular events and gastrointestinal bleeding. The balance between risks and benefits must be evaluated in future studies.

The Proliferation of Paramilitary Groups in Southern Mexico: State Strategy or Struggle between Local Political Elites?

This study traces the origins of Mexican paramilitary groups and argues that, contrary to what most of the literature on the subject implies, they do not represent a state strategy to thwart leftist groups seeking social change. Rather, they represent battles between groups of national and local-level elites with different visions of democracy and of what constitutes good governance. The polarization inherent in this type of conflict leads local actors to have to side with one faction of elites or the other. The presence of radical leftist groups in recently colonized indigenous areas with scant state presence gives rise to a process of radicalization among local elites. There are multiple factors that explain the emergence of paramilitary groups. Aside from the post Cold War international context, there were national factors like a shift in its focus away from security matters between 1989 and 1993, and presidential policies between 1968 and 1993, that planted the seeds of leftist radicalism in a context of id modernization

A "Trojan horse" strategy to reverse drug-resistance in brain tumors

Los gliomas malignos representan una de las formas más agresivas de los tumores del sistema nervioso central (SNC). De acuerdo con la clasificación de los tumores cerebrales de la Organización Mundial de la Salud (OMS), los astrocitomas han sido categorizados en cuatro grados, determinados por la patología subyacente. Es así como los gliomas malignos (o de alto grado) incluyen el glioma anaplásico (grado III) así como el glioblastoma multiforme (GBM, grado IV),estos últimos los más agresivos con el peor pronóstico (1). El manejo terapéutico de los tumores del SNC se basa en la cirugía, la radioterapia y la quimioterapia, dependiendo de las características del tumor, el estadio clínico y la edad (2),(3), sin embargo ninguno de los tratamientos estándar es completamente seguro y compatible con una calidad de vida aceptable (3), (4). En general, la quimioterapia es la primera opción en los tumores diseminados, como el glioblastoma invasivo y el meduloblastoma de alto riesgo o con metástasis múltiple, pero el pronóstico en estos pacientes es muy pobre (2),(3). Solamente nuevas terapias dirigidas (2) como las terapias anti-angiogénicas (4); o terapias génicas muestran un beneficio real en grupos limitados de pacientes con defectos moleculares específicos conocidos (4). De este modo, se hace necesario el desarrollo de nuevas terapias farmacológicas para atacar los tumores cerebrales. Frente a las terapias los gliomas malignos son con frecuencia quimioresistentes, y esta resistencia parece depender de al menos dos mecanismos: en primer lugar, la pobre penetración de muchas drogas anticáncer a través de la barrera hematoencefálica (BBB: Blood Brain Barrier), la barrera del fluido sangre-cerebroespinal (BCSFB: Blood-cerebrospinal fluid barrier) y la barrera sangre-tumor (BTB: blood-tumor barrier). Dicha resistencia se debe a la interacción de la droga con varios transportadores o bombas de eflujo de droga ABC (ABC: ATP-binding cassette) que se sobre expresan en las células endoteliales o epiteliales de estas barreras. En segundo lugar, estos transportadores de eflujo de drogas ABC propios de las células tumorales confieren un fenotipo conocido como resistencia a multidrogas (MDR: multidrug resistance), el cual es característico de varios tumores sólidos. Este fenotipo también está presente en los tumores del SNC y su papel en gliomas es objeto de investigación (5). Por consiguiente el suministro de medicamentos a través de la BBB es uno de los problemas vitales en los tratamientos de terapia dirigida. Estudios recientes han demostrado que algunas moléculas pequeñas utilizadas en estas terapias son sustratos de la glicoproteína P (Pgp: P-gycoprotein), así como también de otras bombas de eflujo como las proteínas relacionadas con la resistencia a multidrogas (MRPs: multidrug resistance-related proteins (MRPs) o la proteína relacionada con cáncer de seno (BCRP: breast-cancer resistance related protein)) que no permiten que las drogas de este tipo alcancen el tumor (1). Un sustrato de Pgp y BCRP es la DOXOrubicina (DOXO), un fármaco utilizado en la terapia anti cáncer, el cual es muy eficaz para atacar las células del tumor cerebral in vitro, pero con un uso clínico limitado por la poca entrega a través de la barrera hematoencefálica (BBB) y por la resistencia propia de los tumores. Por otra parte las células de BBB y las células del tumor cerebral tienen también proteínas superficiales, como el receptor de la lipoproteína de baja densidad (LDLR), que podría utilizarse como blanco terapéutico en BBB y tumores cerebrales. Es asi como la importancia de este estudio se basa en la generación de estrategias terapéuticas que promuevan el paso de las drogas a través de la barrera hematoencefalica y tumoral, y a su vez, se reconozcan mecanismos celulares que induzcan el incremento en la expresión de los transportadores ABC, de manera que puedan ser utilizados como blancos terapéuticos.Este estudio demostró que el uso de una nueva estrategia basada en el “Caballo de Troya”, donde se combina la droga DOXOrubicina, la cual es introducida dentro de un liposoma, salvaguarda la droga de manera que se evita su reconocimiento por parte de los transportadores ABC tanto de la BBB como de las células del tumor. La construcción del liposoma permitió utilizar el receptor LDLR de las células asegurando la entrada a través de la BBB y hacia las células tumorales a través de un proceso de endocitosis. Este mecanismo fue asociado al uso de estatinas o drogas anticolesterol las cuales favorecieron la expresión de LDLR y disminuyeron la actividad de los transportadores ABC por nitración de los mismos, incrementando la eficiencia de nuestro Caballo de Troya. Por consiguiente demostramos que el uso de una nueva estrategia o formulación denominada ApolipoDOXO más el uso de estatinas favorece la administración de fármacos a través de la BBB, venciendo la resistencia del tumor y reduciendo los efectos colaterales dosis dependiente de la DOXOrubicina. Además esta estrategia del "Caballo de Troya", es un nuevo enfoque terapéutico que puede ser considerado como una nueva estrategia para aumentar la eficacia de diferentes fármacos en varios tumores cerebrales y garantiza una alta eficiencia incluso en un medio hipóxico,característico de las células cancerosas, donde la expresión del transportador Pgp se vió aumentada. Teniendo en cuenta la relación entre algunas vías de señalización reconocidas como moduladores de la actividad de Pgp, este estudio presenta no solo la estrategia del Caballo de Troya, sino también otra propuesta terapéutica relacionada con el uso de Temozolomide más DOXOrubicina. Esta estrategia demostró que el temozolomide logra penetrar la BBB por que interviene en la via de señalización de la Wnt/GSK3/β-catenina, la cual modula la expresión del transportador Pgp. Se demostró que el TMZ disminuye la proteína y el mRNA de Wnt3 permitiendo plantear la hipótesis de que la droga al disminuir la transcripción del gen Wnt3 en células de BBB, incrementa la activación de la vía fosforilando la β-catenina y conduciendo a disminuir la β-catenina nuclear y por tanto su unión al promotor del gen mdr1. Con base en los resultados este estudio permitió el reconocimiento de tres mecanismos básicos relacionados con la expresión de los transportadores ABC y asociados a las estrategias empleadas: el primero fue el uso de las estatinas, el cual condujo a la nitración de los transportadores disminuyendo su actividad por la via del factor de transcripción NFκB; el segundo a partir del uso del temozolomide, el cual metila el gen de Wnt3 reduciendo la actividad de la via de señalización de la la β-catenina, disminuyendo la expresión del transportador Pgp. El tercero consistió en la determinación de la relación entre el eje RhoA/RhoA quinasa como un modulador de la via (no canónica) GSK3/β-catenina. Se demostró que la proteína quinasa RhoA promovió la activación de la proteína PTB1, la cual al fosforilar a GSK3 indujo la fosforilación de la β-catenina, lo cual dio lugar a su destrucción por el proteosoma, evitando su unión al promotor del gen mdr1 y por tanto reduciendo su expresión. En conclusión las estrategias propuestas en este trabajo incrementaron la citotoxicidad de las células tumorales al aumentar la permeabilidad no solo de la barrera hematoencefálica, sino también de la propia barrera tumoral. Igualmente, la estrategia del “Caballo de Troya” podría ser útil para la terapia de otras enfermedades asociadas al sistema nervioso central. Por otra parte estos estudios indican que el reconocimiento de mecanismos asociados a la expresión de los transportadores ABC podría constituir una herramienta clave en el desarrollo de nuevas terapias anticáncer.

Treatment of mature urban landfill leachates by anammox process

This thesis results from the collaborative projects between the LEQUIA-UdG group and Cespa (a company in charge of several landfill sites in Spain). The aim of the work was the development of a suitable alternative treatment for nitrogen removal from mature landfill leachates. The thesis presents the application of the anammox (anaerobic ammonium oxidation process) process to treat ammonium rich leachates as the second step of the PANAMMOX® process. The work deals with preliminary studies about the characteristics of the anammox process in a SBR, with special focus on the response of the biomass to nitrite exposure. The application of the anammox process with leachate was first studied in a lab-scale reactor, to test the effect of the leachate matrix on anammox biomass and its progressive adaptation. Finally, a start-up strategy is developed and applied for the successful start-up of a 400L anammox SBR in less than 6 months.

Century-of-Information Research (CIR): a strategy for research and innovation in the century of information

More data will be produced in the next five years than in the entire history of human kind, a digital deluge that marks the beginning of the Century of Information. Through a year-long consultation with UK researchers, a coherent strategy has been developed, which will nurture Century-of-Information Research (CIR); it crystallises the ideas developed by the e-Science Directors' Forum Strategy Working Group. This paper is an abridged version of their latest report which can be found at: http://wikis.nesc.ac.uk/escienvoy/Century_of_Information_Research_Strategy which also records the consultation process and the affiliations of the authors. This document is derived from a paper presented at the Oxford e-Research Conference 2008 and takes into account suggestions made in the ensuing panel discussion. The goals of the CIR Strategy are to facilitate the growth of UK research and innovation that is data and computationally intensive and to develop a new culture of 'digital-systems judgement' that will equip research communities, businesses, government and society as a whole, with the skills essential to compete and prosper in the Century of Information. The CIR Strategy identifies a national requirement for a balanced programme of coordination, research, infrastructure, translational investment and education to empower UK researchers, industry, government and society. The Strategy is designed to deliver an environment which meets the needs of UK researchers so that they can respond agilely to challenges, can create knowledge and skills, and can lead new kinds of research. It is a call to action for those engaged in research, those providing data and computational facilities, those governing research and those shaping education policies. The ultimate aim is to help researchers strengthen the international competitiveness of the UK research base and increase its contribution to the economy. The objectives of the Strategy are to better enable UK researchers across all disciplines to contribute world-leading fundamental research; to accelerate the translation of research into practice; and to develop improved capabilities, facilities and context for research and innovation. It envisages a culture that is better able to grasp the opportunities provided by the growing wealth of digital information. Computing has, of course, already become a fundamental tool in all research disciplines. The UK e-Science programme (2001-06)—since emulated internationally—pioneered the invention and use of new research methods, and a new wave of innovations in digital-information technologies which have enabled them. The Strategy argues that the UK must now harness and leverage its own, plus the now global, investment in digital-information technology in order to spread the benefits as widely as possible in research, education, industry and government. Implementing the Strategy would deliver the computational infrastructure and its benefits as envisaged in the Science & Innovation Investment Framework 2004-2014 (July 2004), and in the reports developing those proposals. To achieve this, the Strategy proposes the following actions: support the continuous innovation of digital-information research methods; provide easily used, pervasive and sustained e-Infrastructure for all research; enlarge the productive research community which exploits the new methods efficiently; generate capacity, propagate knowledge and develop skills via new curricula; and develop coordination mechanisms to improve the opportunities for interdisciplinary research and to make digital-infrastructure provision more cost effective. To gain the best value for money strategic coordination is required across a broad spectrum of stakeholders. A coherent strategy is essential in order to establish and sustain the UK as an international leader of well-curated national data assets and computational infrastructure, which is expertly used to shape policy, support decisions, empower researchers and to roll out the results to the wider benefit of society. The value of data as a foundation for wellbeing and a sustainable society must be appreciated; national resources must be more wisely directed to the collection, curation, discovery, widening access, analysis and exploitation of these data. Every researcher must be able to draw on skills, tools and computational resources to develop insights, test hypotheses and translate inventions into productive use, or to extract knowledge in support of governmental decision making. This foundation plus the skills developed will launch significant advances in research, in business, in professional practice and in government with many consequent benefits for UK citizens. The Strategy presented here addresses these complex and interlocking requirements.

Risk and price in the bidding process of contractors

Formal and analytical risk models prescribe how risk should be incorporated in construction bids. However, the actual process of how contractors and their clients negotiate and agree on price is complex, and not clearly articulated in the literature. Using participant observation, the entire tender process was shadowed in two leading UK construction firms. This was compared to propositions in analytical models and significant differences were found. 670 hours of work observed in both firms revealed three stages of the bidding process. Bidding activities were categorized and their extent estimated as deskwork (32%), calculations (19%), meetings (14%), documents (13%), off-days (11%), conversations (7%), correspondence (3%) and travel (1%). Risk allowances of 1-2% were priced in some bids and three tiers of risk apportionment in bids were identified. However, priced risks may sometimes be excluded from the final bidding price to enhance competitiveness. Thus, although risk apportionment affects a contractor’s pricing strategy, other complex, microeconomic factors also affect price. Instead of pricing in contingencies, risk was priced mostly through contractual rather than price mechanisms, to reflect commercial imperatives. The findings explain why some assumptions underpinning analytical models may not be sustainable in practice and why what actually happens in practice is important for those who seek to model the pricing of construction bids.

Dynamics and foraging behaviour of adult hornet robberflies, Asilus crabroniformis: implications for conservation strategy

Mark resighting studies of the hornet robberfly, Asilus crabroniformis, were carried out during the flight seasons of 1999 and 2000 on agricultural land on the Chilterns in Oxfordshire, UK. Six patches of land were identified which contained characteristics thought to be attractive to hornet robberflies. One hundred and twenty eight adults were marked in 1999 and 257 in 2000. Marking was carried out on one of the patches, but resighting observations were collected from all six sites. The daily population sizes were estimated using the Jolly-Seber method. The daily population size peaked between 50 and 72 from 23 August until 13 September in 2000. This was very similar to the peak population size of between 50 and 74 estimated for 1999. Adults were found to be capable of living for nearly 5 weeks. The maximum linear distance from the point of marking that any individual moved across the study site was 625 m, but some individuals moved over 400 m in a single day. Unsuitable habitat (suburban gardens and a main road) did not present a barrier to dispersal. Males were more likely than females to loiter in sites peripheral to the breeding site, whilst females seemed to be more tied to the breeding site. Most adults were caught from dung piles, but insects avoided fresh dung and preferred instead dung that was well into the process of drying out. A variety of insect species were taken as prey, including many beetles and flies. The findings of the study are discussed in relation to the management of the landscape to enhance the long-term prospects of the hornet robberfly in the UK, and to achieve the UK Biodiversity Action Plan target for this species.

A new strategy for the blind MMSE equalization

This paper describes a new strategy for the blind equalization so that the blind Constant Module Algorithm (CMA) can be smoothly switched to the decision- directed (DD) equalization. First, we propose a combination approach by running the CMA and DD equalization simultaneously to obtain a smooth switch between them. We then describe an "anchoring process" to eliminate the effect from the CMA at the steady state to achieve low residual noise. The overall equalization can be regarded as the DD equalization being anchored by the combination approach. Numerical simulations are given to verify the proposed strategy.

Corporate social responsibility in construction and engineering firms: key elements of effective strategy

Through multiple case studies of firms we argue that firms that have developed corporate responsibility strategies, albeit informally at first, do so by making intentional, informed and collective choices about CSR initiatives. More precisely, we point to the importance of considering corporate identity in making these choices and to the process of adaptive coordination, which includes both responding to and influencing the CSR environment. We conclude that CSR strategic landscape are determined more and more by the astute and careful management of a network of cooperative and competitive stakeholder interests which possess both tangible and intangible value to a firm.

Striving for inclusive design in the built environment: learning strategy adopted by policy implementers at local authorities in England

The research will explore views on inclusive design policy implementation and learning strategy used in practice by Local Authorities’ planning, building control and policy departments in England. It reports emerging research findings. The research aim was developed from an extensive literature review, and informed by a pilot study with relevant Local Authority departments. The pilot study highlighted gaps within the process of policy implementation, a lack of awareness of the process and flaws in the design guidance policy. This has helped inform the development of a robust research design using both a survey and semi-structured interviews. The questionnaire targeted key employees within Local Authorities designed to establish how employees learn about inclusive design policy and to determine their views on current approaches of inclusive design policy implementation adopted by their Local Authorities. The questionnaire produces 117 responses. Interestingly approximately 9 out of 129 Local Authorities approached claimed that they were unable to participate either because an inclusive design policy was not adopted or they were faced with a high workload and thus unable to take part. An emerging finding is a lack of understanding of inclusive design problems, which may lead to problem with inclusive design policy implementation, and thus adversely affect how the built environment can be experienced. There is a strong indication from the survey respondents indicating that they are most likely to learn about inclusive design from policy guides produced by their Local Authorities and from their colleagues.

Modeling growth strategy in a biotechnology startup firm

The top managers of a biotechnology startup firm agreed to participate in a system dynamics modeling project to help them think about the firm's growth strategy. The article describes how the model was created and used to stimulate debate and discussion about growth management. The paper highlights several novel features about the process used for capturing management team knowledge. A heavy emphasis was placed on mapping the operating structure of the factory and distribution channels. Qualitative modeling methods (structural diagrams, descriptive variable names, and friendly algebra) were used to capture the management team's descriptions of the business. Simulation scenarios were crafted to stimulate debate about strategic issues such as capacity allocation, capacity expansion, customer recruitment, customer retention, and market growth, and to engage the management team in using the computer to design strategic scenarios. The article concludes with comments on the impact of the project.

Living to die and dying to live: the survival strategy behind leaf senescence

Senescence represents the final developmental act of the leaf, during which the leaf cell is dismantled in a coordinated manner to remobilize nutrients and to secure reproductive success. The process of senescence provides the plant with phenotypic plasticity to help it adapt to adverse environmental conditions. Here, we provide a comprehensive overview of the factors and mechanisms that control the onset of senescence. We explain how the competence to senesce is established during leaf development, as depicted by the senescence window model. We also discuss the mechanisms by which phytohormones and environmental stresses control senescence, as well as the impact of source-sink relationships on plant yield and stress tolerance. In addition, we discuss the role of senescence as a strategy for stress adaptation and how crop production and food quality could benefit from engineering or breeding crops with altered onset of senescence.

Bank regulation and the process of internationalisation: a study of Japanese bank entry into London

The paper provides a theoretical insight into bank regulation and the process of internationalisation by examining the concepts of regulatory push and market pull within the context of Japanese bank entry into London during the 1980s. Rugman and Verbeke's [(1998). Corporate strategy and international environmental policy. Journal of International Business Studies, 29(4), 819–833] Consistency of Home and Host Government Goals model is utilised to structure the discussion, which centres on a situation where there is a conflict of goals between multinational enterprises (MNEs) and the home government but goal alignment between MNEs and the host government. As such the paper examines a relatively under-researched aspect of internationalisation and concludes that in certain circumstances internationalisation can occur despite great ‘psychic distance’. The paper also argues that although bank regulation can lead to a conflict situation it can also be conducive to the development of a strong home base and the development of firm specific advantages.

Attractive Work Process

Many companies both in Sweden and other parts of the world are since the beginning of the 21st century faceing a lack of work force (1,2,3). The ability to recruit and retain skilled employees is seen as one of the most important questions for the survival and development of the companies (4,5). Labour shortage is seen as the biggest obstacle for expansion for small enterprises in Sweden (5). There is a need for workplaces to be attractive, but how can the attractiveness be increased? Researchers at Högskolan Dalarna have during almost a decennium conducted research concerning attractive work. Based on a modell of qualities that contributes to make a work attractive (6) has a method aiming for raised attractiveness been developed for SME:s. All employees participate by answering a questionnaire about the importance of different qualities and to what degree they are fulfilled. Further discussions at the workplace on what to preserve and what to develop make the base for an action plan.Important experiences:• Discuss and establish the aim of the method with management and employees. • The company must be prepared to follow up and realize the action plan.• Agree about expectations – they must be realistic and practicable.• Reserve time to start the process and to end up in an action plan. • Avoid negative thinking and put problems away. • Take all the time small steps in the right direction.• Keep employees engaged and avoid the manager or process leader to take the command.• Use the strategy with small work groups; it gives better possibilities for participation and outspokenness.• Follow up studies are necessary to keep up the motivation.The most positive aspects of the method is its promoting perspective and that it engages all the employees.1.Rauhut, D. (2002). Arbetskraftsbrist och arbetskraftsinvandring: hot eller möjlighet för ekonomisk tillväxt? Östersund, ITPS, Institutet för tillväxtpolitiska studier.2.Funch, M. and C. Ehrnooth. (2008, 08-10-2008). Labour shortage despite financial crisis? Retrieved 2008-12-16, 2008, from www.norden.org/webb/news/news.asp?id=8113&lang=6. 3.Manpower (2008). Talent Shortage Survey 2008 Global Results: 10. 4.Bakker, A. B. and W. B. Schaufeli (2008). Positive organizational behavior: Engaged employees in flourishing organizations. Journal of Organizational Behavior 29: 147-154.5.Kennemar, J. and L. Jagrén (2008). Småföretagsbarometern. Stockholm, Swedbank Företagarna: 23.6.Åteg, M., A. Hedlund, et al. (2004). Attraktivt arbete. Från anställdas uttalanden till skapandet av en modell. Stockholm, Arbetslivsinstitutet.