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Selected AbstractsThe merging of community ecology and phylogenetic biologyECOLOGY LETTERS, Issue 7 2009Jeannine Cavender-Bares Abstract The increasing availability of phylogenetic data, computing power and informatics tools has facilitated a rapid expansion of studies that apply phylogenetic data and methods to community ecology. Several key areas are reviewed in which phylogenetic information helps to resolve long-standing controversies in community ecology, challenges previous assumptions, and opens new areas of investigation. In particular, studies in phylogenetic community ecology have helped to reveal the multitude of processes driving community assembly and have demonstrated the importance of evolution in the assembly process. Phylogenetic approaches have also increased understanding of the consequences of community interactions for speciation, adaptation and extinction. Finally, phylogenetic community structure and composition holds promise for predicting ecosystem processes and impacts of global change. Major challenges to advancing these areas remain. In particular, determining the extent to which ecologically relevant traits are phylogenetically conserved or convergent, and over what temporal scale, is critical to understanding the causes of community phylogenetic structure and its evolutionary and ecosystem consequences. Harnessing phylogenetic information to understand and forecast changes in diversity and dynamics of communities is a critical step in managing and restoring the Earth's biota in a time of rapid global change. [source] Taking stem cells to the clinic: Major challengesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Ariff Bongso Abstract Stem cell therapy offers tremendous promise in the treatment of many incurable diseases. A variety of stem cell types are being studied but human embryonic stem cells (hESCs) appear to be the most versatile as they are pluripotent and can theoretically differentiate into all the tissues of the human body via the three primordial germ layers and the male and female germ lines. Currently, hESCs have been successfully converted in vitro into functional insulin secreting islets, cardiomyocytes, and neuronal cells and transfer of such cells into diabetic, ischaemic, and parkinsonian animal models respectively have shown successful engraftment. However, hESC-derived tissue application in the human is fraught with the problems of ethics, immunorejection, tumorigenesis from rogue undifferentiated hESCs, and inadequate cell numbers because of long population doubling times in hESCs. Human mesenchymal stem cells (hMSC) though not tumorigenic, also have their limitations of multipotency, immunorejection, and are currently confined to autologous transplantation with the genuine benefits in allogeneic settings not conclusively shown in large controlled human trials. Human Wharton's jelly stem cells (WJSC) from the umbilical cord matrix which are of epiblast origin and containing both hESC and hMSC markers appear to be less troublesome in not being an ethically controversial source, widely multipotent, not tumorigenic, maintain "stemness" for several serial passages and because of short population doubling time can be scaled up in large numbers. This report describes in detail the hurdles all these stem cell types have to overcome before stem cell-based therapy becomes a genuine reality. J. Cell. Biochem. 105: 1352,1360, 2008. © 2008 Wiley-Liss, Inc. [source] Review: Microscale methods for high-throughput chromatography development in the pharmaceutical industryJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 7 2009Sunil Chhatre Abstract Demands within the pharmaceutical sector to cut costs and improve process efficiencies have grown considerably in recent years. Major challenges exist for companies trying to establish financially viable and robust manufacturing processes for increasingly complex therapeutics. These issues have driven the investigation of miniaturised process-design techniques by which to identify suitable operating conditions using small volumes of feed material typical of that available in the early stages of bioprocess development. Such techniques are especially valuable for the optimisation of chromatographic separations, which often represent a significant percentage of manufacturing costs and hence for which there is a pressing need to determine the best operating policies. Several methods employing microlitre volumes of sample and resin have been explored recently, which are aimed at the high-throughput and cost-effective exploration of the design space for chromatographic separations. This methodology paper reviews these microscale approaches and describes how they work, gives examples of their application, discusses their advantages and disadvantages and provides a comparative assessment of the different methods, along with a summary of the challenges that remain to be overcome in relation to these techniques. Copyright © 2009 Society of Chemical Industry [source] Creating a Shared Formulary in 7 Critical Access HospitalsTHE JOURNAL OF RURAL HEALTH, Issue 3 2010Douglas S. Wakefield PhD Abstract Purpose: This paper reports a case study of 7 Critical Access Hospitals' (CAH) and 1 rural referral hospital's successful collaboration to develop a shared formulary. Methods: Study methods included document reviews, interviews with key informants, and use of descriptive statistics. Findings: Through a systematic review and decision process, CAH formularies ranging in size from 667 to 1,351 items were compared, rationalized, and consolidated resulting in an 803-item shared formulary. While the individual CAHs were generally expected to list and stock the same 803 items in the shared formulary's pharmacy information system, they could individually determine the amount to be stocked for each item, as well as stock additional items not included on the shared formulary to reflect local provider preferences and services provided. Final stocked formulary items ranged from 592 to 786 items among the 7 CAHs. Major challenges and lessons learned in the course of developing a shared formulary related to: Meeting Logistics, Facilitator to Manage the Process, Organizing the Review Process, Management Support, Stakeholder Participation, Working Collaboratively, Decision-Making Process, Clarity of Charge, Meeting the Needs of Unique Services, Communicating with Providers, and Adjusting to a Shared Formulary. Conclusions: Collaborating in the development of a shared formulary allows for a greater range of decision-making expertise, shared workload, and an improved formulary. An organized and well-managed group decision-making process is essential to a successful collaboration. [source] Interactive animation of cloth-like objects in virtual realityCOMPUTER ANIMATION AND VIRTUAL WORLDS (PREV: JNL OF VISUALISATION & COMPUTER ANIMATION), Issue 1 2001Mark Meyer Abstract Modeling and animation of cloth have experienced important developments in recent years. As a consequence, complex textile models can be used to realistically drape objects or human characters in a fairly efficient way. However, real-time realistic simulation remains a major challenge, even if applications are numerous, from rapid prototyping to e-commerce. In this paper, we present a stable, real-time algorithm for animating cloth-like materials. Using a hybrid explicit/implicit algorithm, we perform fast and stable time integration of a physically based model with rapid collision detection and response, as well as wind or liquid drag effects to enhance realism. We demonstrate our approach through a series of examples in virtual reality environments, proving that real-time animation of cloth, even on low-end computers, is now achievable. Copyright © 2001 John Wiley & Sons, Ltd. [source] Confronting Uncertainty and Missing Values in Environmental Value Transfer as Applied to Species ConservationCONSERVATION BIOLOGY, Issue 5 2010SONIA AKTER conservación de especies; error de transferencia; incertidumbre; transferencia de valor ambiental; valores de no uso Abstract:,The nonuse (or passive) value of nature is important but time-consuming and costly to quantify with direct surveys. In the absence of estimates of these values, there will likely be less investment in conservation actions that generate substantial nonuse benefits, such as conservation of native species. To help overcome decisions about the allocation of conservation dollars that reflect the lack of estimates of nonuse values, these values can be estimated indirectly by environmental value transfer (EVT). EVT uses existing data or information from a study site such that the estimated monetary value of an environmental good is transferred to another location or policy site. A major challenge in the use of EVT is the uncertainty about the sign and size of the error (i.e., the percentage by which transferred value exceeds the actual value) that results from transferring direct estimates of nonuse values from a study to a policy site, the site where the value is transferred. An EVT is most useful if the decision-making framework does not require highly accurate information and when the conservation decision is constrained by time and financial resources. To account for uncertainty in the decision-making process, a decision heuristic that guides the decision process and illustrates the possible decision branches, can be followed. To account for the uncertainty associated with the transfer of values from one site to another, we developed a risk and simulation approach that uses Monte Carlo simulations to evaluate the net benefits of conservation investments and takes into account different possible distributions of transfer error. This method does not reduce transfer error, but it provides a way to account for the effect of transfer error in conservation decision making. Our risk and simulation approach and decision-based framework on when to use EVT offer better-informed decision making in conservation. Resumen:,El valor de no uso (o pasivo) de la naturaleza es importante pero su cuantificación con muestreos pasivos consume tiempo y es costosa. En ausencia de estimaciones de estos valores, es probable que haya menos inversión en acciones de conservación que generen beneficios de no uso sustanciales, tal como la conservación de especies nativas. Para ayudar a superar decisiones respecto a la asignación de dólares para conservación que reflejan la carencia de estimaciones de los valores de no uso, estos valores pueden ser estimados indirectamente por la transferencia de valor ambiental (TVA). La transferencia de valor ambiental utiliza datos existentes o información de un sitio de estudio de tal manera que el valor monetario estimado de un bien ambiental es transferido a otro sitio. Un reto mayor en el uso de TVA es la incertidumbre sobre la señal y el tamaño del error (i.e., el porcentaje en que el valor transferido excede al valor actual) que resulta de la transferencia de estimaciones directas de los valores de no uso de un sitio de estudio a uno político, el sitio adonde el valor es transferido. Una TVA es más útil si el marco de toma de decisiones no requiere información muy precisa y cuando la decisión de conservación está restringida por tiempo y recursos financieros. Para tomar en cuenta la incertidumbre en el proceso de toma de decisiones, se puede seguir una decisión heurística que guie el proceso de decisión e ilustre sobre las posibles ramificaciones de la decisión. Para tomar en cuenta la incertidumbre asociada con la transferencia de valores de un sitio a otro, desarrollamos un método de riesgo y simulación que utiliza simulaciones Monte Carlo para evaluar los beneficios netos de las inversiones de conservación y que considera posibles distribuciones diferentes de la transferencia de error. Este método no reduce el error de transferencia, pero proporciona una manera para considerar el efecto del error de transferencia en la toma de decisiones de conservación. Nuestro método de riesgo y simulación y el marco de referencia basado en decisones sobre cuando utilizar TVA permiten la toma de decisiones en conservación más informadas. [source] Nonindigenous Species: Ecological Explanation, Environmental Ethics, and Public PolicyCONSERVATION BIOLOGY, Issue 1 2003David M. Lodge Misunderstandings and tension exist regarding the science, values, environmental ethics, and public policy relevant to invasive species, which are the subset of nonindigenous species that cause economic or environmental damage. Although there is a natural background rate at which species invasions occur, it is much lower than the current human-induced rates at which species are being moved around the globe. Contrary to some recently voiced opinions , the fact that some species invasions occur without human assistance does not confer acceptability on all species invasions. Also, despite claims to the contrary, the reductions of native biodiversity caused by nonindigenous species are large and well documented. Even if that were not true, an emphasis on species numbers alone as a metric for the impact of nonindigenous species does not adequately incorporate the high value many humans place on the uniqueness of regional biota. Because regional biota are being homogenized by species invasions, it has become an appropriate and official public policy goal in the United States to reduce the harm done by invasive species. The goal is not, however, a reduction of numbers of nonindigenous species per se, as recently claimed by some authors, but a reduction in the damage caused by invasive species, including many sorts of environmental and economic damage. A major challenge remaining for ecology, environmental ethics, and public policy is therefore the development of widely applicable risk-assessment protocols that are acceptable to diverse constituencies. Despite apparent disagreements among scholars, little real disagreement exists about the occurrence, effects, or public-policy implications of nonindigenous species. Resumen: El público está recibiendo un mensaje confuso de ecologistas, otros académicos y periodistas sobre el tema de especies no nativas. Existen malos entendidos y tensión en relación con la ciencia, los valores, la ética ambiental y las políticas públicas relevantes a las especies invasoras, que son un subconjunto de las especies no nativas que causan daños económicos o ambientales. Aunque existe una tasa natural a la que ocurren invasiones, es mucho más baja que las actuales tasas, inducidas por humanos, a las que especies son movidas alrededor del mundo. Al contrario de algunos autores recientes, el hecho de que algunas invasiones de especies ocurren sin asistencia humana no le confiere aceptabilidad moral sobre todas las invasiones de especies. También, a pesar de recientes afirmaciones de lo contrario, las reducciones de biodiversidad nativa debido a especies no nativas son notables y están bien documentadas. Aún si no fuera verdad, el énfasis sólo en el número de especies como una medida del impacto de especies no nativas no incorpora adecuadamente el alto valor que muchos humanos reconocen en la singularidad de la biota regional. Debido a que la biota regional está siendo homogeneizada por invasiones de especies, la reducción del daño causado por especies invasoras se ha convertido en una política pública apropiada y oficial en los Estados Unidos. Sin embargo, la meta no es la reducción de especies no nativas, en si, como afirman algunos autores recientes, sino una reducción de los impactos dañinos de las especies invasoras, incluyendo muchos tipos de daño económico y ambiental. Por lo tanto, un reto mayor para la ecología, la ética ambiental y la política pública es el desarrollo de protocolos de evaluación de riesgos ampliamente aplicables que sean aceptables para electores diversos. A pesar de aparentes desacuerdos entre académicos, existe poco desacuerdo real acerca de la ocurrencia, el impacto o las implicancias en política pública de las especies no nativas. [source] Nonablative Acne Scar Reduction after a Series of Treatments with a Short-Pulsed 1,064-nm Neodymium:YAG LaserDERMATOLOGIC SURGERY, Issue 8 2006GRAEME M. LIPPER MD BACKGROUND Effective treatment of facial acne scarring presents a major challenge. Nonablative lasers and radiofrequency devices work by thermally stimulating dermal collagen remodeling, thereby softening acne scars in a minimally invasive fashion. One such laser, a 1,064-nm short-pulsed Nd:YAG, uses rapidly scanned low-energy infrared pulses to heat the dermis selectively through the normal dermal microvasculature. OBJECTIVE In this pilot study, the safety and efficacy of a novel short-pulsed Nd:YAG laser were investigated for the treatment of moderate to severe facial acne scarring. MATERIALS AND METHODS Nine of 10 enrolled patients with moderate to severe facial acne scarring received eight sequential 1,064-nm Nd:YAG treatments (laser parameters 14 J/cm2, 0.3 milliseconds, 5-mm spot size, 7-Hz pulse rate, 2,000 pulses per side of face). Patients were graded for the presence and severity of three scar morphologies: superficial (rolling), medium-depth (boxcar), and deep (ice pick). Outcome measures included blinded evaluation of before and after photographs by three physician observers (scar severity score) and patient self-assessment. RESULTS Acne scarring improved in 100% of the nine patients completing the study. Scar severity scores improved by a mean of 29.36% (95% confidence interval, 16.93%,41.79%; p=.006); 89% of patients noted greater than 10% scar improvement. No treatment-related adverse events were seen. CONCLUSION Our findings support the use of a short-pulsed, low-fluence 1,064-nm Nd:YAG laser as a safe, effective treatment for facial acne scarring. Scar improvement was noted in all treated subjects with minimal discomfort and no downtime. This protocol appears to be most effective at reducing scar depth and softening scar contours. [source] ,-cell development: the role of intercellular signalsDIABETES OBESITY & METABOLISM, Issue 2008R. Scharfmann Understanding in detail how pancreatic endocrine cells develop is important for many reasons. From a scientific point of view, elucidation of such a complex process is a major challenge. From a more applied point of view, this may help us to better understand and treat specific forms of diabetes. Although a variety of therapeutic approaches are well validated, no cure for diabetes is available. Many arguments indicate that the development of new strategies to cure diabetic patients will require precise understanding of the way ,-cells form during development. This is obvious for a future cell therapy using ,-cells produced from embryonic stem cells. This also holds true for therapeutic approaches based on regenerative medicine. In this review, we summarize our current knowledge concerning pancreatic development and focus on the role of extracellular signals implicated in ,-cell development from pancreatic progenitors. [source] Role of histone and transcription factor acetylation in diabetes pathogenesisDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2005Steven G. Gray Abstract Globally, diabetes (and, in particular, type 2 diabetes) represents a major challenge to world health. Currently in the United States, the costs of treating diabetes and its associated complications exceed $100 billion annually, and this figure is expected to soar in the near future. Despite decades of intense research efforts, the genetic basis of the events involved in the pathogenesis of diabetes is still poorly understood. Diabetes is a complex multigenic syndrome primarily due to beta-cell dysfunction associated with a variable degree of insulin resistance. Recent advances have led to exciting new developments with regard to our understanding of the mechanisms that regulate insulin transcription. These include data that implicate chromatin as a critical regulator of this event. The ,Histone Code' is a widely accepted hypothesis, whereby sequential modifications to the histones in chromatin lead to regulated transcription of genes. One of the modifications used in the histone code is acetylation. This is probably the best characterized modification of histones, which is carried out under the control of histone acetyltransferases (HATs) and histone deacetylases (HDACs). These enzymes also regulate the activity of a number of transcription factors through acetylation. Increasing evidence links possible dysregulation of these mechanisms in the pathogenesis of diabetes, with important therapeutic implications. Copyright © 2005 John Wiley & Sons, Ltd. [source] The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursorsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2004Laura Wilding Abstract Ex vivo expansion of embryonic stem cells (ES cells) or pancreatic stem cells for insulin delivery to diabetic patients provides potential for the restoration of islet function in these individuals. Understanding the spatial and temporal requirements of crucial factors for endocrine progenitor specification, proliferation, and terminal differentiation remains a major challenge in the field of pancreas development. Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. The current body of evidence provides support for a role of both factors in early endocrine specification as well as a requirement for pdx1 in the generation of mature pancreatic endocrine cells. The precise temporal requirement of HNF6 in the production of terminally differentiated endocrine cells remains unclear. Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. Copyright © 2004 John Wiley & Sons, Ltd. [source] Resilience of tropical rain forests: tree community reassembly in secondary forestsECOLOGY LETTERS, Issue 5 2009Natalia Norden Abstract Understanding the recovery dynamics of ecosystems presents a major challenge in the human-impacted tropics. We tested whether secondary forests follow equilibrium or non-equilibrium dynamics by evaluating community reassembly over time, across different successional stages, and among multiple life stages. Based on long-term and static data from six 1-ha plots in NE Costa Rica, we show that secondary forests are undergoing reassembly of canopy tree and palm species composition through the successful recruitment of seedlings, saplings, and young trees of mature forest species. Such patterns were observed over time within sites and across successional stages. Floristic reassembly in secondary forests showed a clear convergence with mature forest community composition, supporting an equilibrium model. This resilience stems from three key factors co-occurring locally: high abundance of generalist species in the regional flora, high levels of seed dispersal, and local presence of old-growth forest remnants. [source] Electrochemical Biosensors for Detection of Biological Warfare AgentsELECTROANALYSIS, Issue 3 2003Jasmin Shah Abstract This review discusses current development in electrochemical biosensors for detection of biological warfare agents. This could include bacteria, viruses and toxins that are aerosoled deliberately in air, food or water to spread terrorism and cause disease or death to humans, animals or plants. The rapid and unequivocal detection and identification of biological warfare agents is a major challenge for any government including military, health and other government agents. Reliable, specific characterization and identification of the microorganism from sampling location, either air, water, soil or others is required. This review will survey different types of electrochemical biosensors has been developed based on the following: i),Immunosensors ii),PCR (DNA base Sensor) iii),Bacteria or whole cell sensor and iv),Enzyme sensor. This article gives an overview of electrochemical biosensor for detection of biological warfare agents. Electrochemical biosensors have the advantages of sensitivity, selectivity, to operate in turbid media, and amenable to miniaturization. Recent developments in immunofiltration, flow injection, and flow-through electrochemical biosensors for bacteria, viruses, and toxin detection are reviewed. The current research and development in biosensors for biological warfare agents detection is of interest to the public as well as to the defense is also discussed. [source] Numerical studies of electrokinetic control of DNA concentration in a closed-end microchannelELECTROPHORESIS, Issue 5 2010Yasaman Daghighi Abstract A major challenge in lab-on-a-chip devices is how to concentrate sample molecules from a dilute solution, which is critical to the effectiveness and the detection limit of on-chip bio-chemical reactions. A numerical study of sample concentration control by electrokinetic microfluidic means in a closed-end microchannel is presented in this paper. The present method provides a simple and efficient way of concentration control by using electrokinetic trapping of a charged species of interest, controlling liquid flow and separating different sample molecules in the microchannel. The electrokinetic-concentration process and the controlled transport of the sample molecules are numerically studied. In this system, in addition to the electroosmotic flow and the electrophoresis, the closed-end of the chamber causes velocity variation at both ends of the channel and induces a pressure gradient and the associated fluid movement in the channel. The combined effects determine the final concentration field of the sample molecules. The influences of a number of parameters such as the channel dimensions, electrode size and the applied electric field are investigated. [source] An international survey of training programs for treating tobacco dependenceADDICTION, Issue 2 2009Nancy A. Rigotti ABSTRACT Aims The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) requires countries to implement tobacco dependence treatment programs. To provide treatment effectively, a country needs trained individuals to deliver these services. We report on the global status of programs that train individuals to provide tobacco dependence treatment. Design Cross-sectional web-based survey of tobacco treatment training programs in a stratified convenience sample of countries chosen to vary by WHO geographic region and World Bank income level. Participants Key informants in 48 countries; 70% of 69 countries who were sent surveys responded. Measurements Program prevalence, frequency, duration and size; background of trainees; content (adherence to pre-defined core competencies); funding sources; challenges. Findings We identified 61 current tobacco treatment training programs in 37 (77%) of 48 countries responding to the survey. Three-quarters of them began in 2000 or later, and 40% began after 2003, when the FCTC was adopted. Programs estimated training 14 194 individuals in 2007. Training was offered to a variety of professionals and paraprofessionals, but most often to physicians and nurses. Median program duration was 16 hours, but programs' duration, intensity and size varied widely. Most programs used evidence-based guidelines and reported adherence to core tobacco treatment competencies. Training programs were less frequent in low-income countries and in Africa. Securing funding was the major challenge for most programs; current funding sources were government (58%), non-government organizations (23%), pharmaceutical companies (17%) and, in one case, the tobacco industry. Conclusion Training programs for tobacco treatment providers are diverse and growing. Most upper- and middle-income countries have programs, and most programs appear to be evidence-based. However, funding is a major challenge. In particular, more programs are needed for non-physicians and for low-income countries. [source] Lead toxicosis in the horse: A reviewEQUINE VETERINARY EDUCATION, Issue 10 2010B. Puschner Summary Lead intoxication is rarely diagnosed in horses and can present a major challenge to the equine practitioner because of the variety of clinical signs. Horses with lead poisoning can develop gastrointestinal disturbances, neurological abnormalities, haematological changes, or nonspecific signs of weight loss, weakness and rough hair coat, which makes early diagnosis difficult. Fortunately, lead analysis of whole blood is routinely available and can confirm intoxication. Because of the well-described lead-induced peripheral neuropathies in horses, a thorough neurological examination is essential in the investigation of a suspect case. Once diagnosed, the source of lead has to be identified and further exposure prevented. Intoxication can be treated by administering chelating drugs and providing symptomatic and supportive care. [source] Infrastructure and Rural Development: US and EU Perspectives Infrastruktur und Entwicklung des ländlichen Raums: Perspektiven aus den USA und der EU Infrastructures et développement rural : Perspectives aux États-Unis et dans l'Union européenneEUROCHOICES, Issue 1 2008David Blandford Infrastructure and Rural Development: US and EU Perspectives Infrastructural development remains a cornerstone of rural development policy in both the United States and Europe. It is evident that rural development objectives differ, but similar policy measures are used. The economic rationale for infrastructure development centres on efficiency and creation of competitive advantage. Policy intervention is justified because of the added costs of infrastructure provision in remote, sparsely populated areas. Although this policy focus does not guarantee success, regions leading in economic development typically have better physical infrastructure. In the United States, policy must adapt to challenges posed by an ageing rural infrastructure and demographic change that will increase demands on social infrastructure such as housing and health facilities. There will be greater local responsibility for funding, and expanded use of public/private partnerships. In the European Union, the major challenge is in redirecting resources to new member states, where there is urgent need for both large new investments in transport networks and small investments to improve local access. Although two current options for funding these diverse needs focus on European policies only, investments in non-farm physical capital and public infrastructure cannot be sustained without active national policies to complement the European efforts, perhaps through co-financing requirements. Infrastructures et développement rural : Perspectives aux États-Unis et dans l'Union européenne Le développement des infrastructures demeure un pilier de la politique de développement rural aux États-Unis comme dans l'Union européenne. Les objectifs de développement rural diffèrent bien évidemment mais des mesures semblables sont employées. La justification économique du développement des infrastructures repose sur l'efficience et la création d'avantages concurrentiels. L'intervention publique est justifiée par les coûts supplémentaires des infrastructures dans les zones éloignées à population clairsemée. Bien que ce type de politique ne garantisse pas le succès, les régions en avance de développement économique ont en général de meilleures infrastructures physiques. Aux États-Unis, la politique soit s'adapter aux défis que posent le vieillissement des infrastructures rurales et l'évolution démographique qui va augmenter la demande d'infrastructures sociales telles que les services de santé et de logement. La responsabilité du financement local va augmenter et les partenariats public/privé vont se développer. Dans l'Union européenne, le principal défi est de réorienter les ressources vers les nouveaux pays membres qui ont un besoin urgent de nouveaux investissement d'ampleur dans les réseaux de transport et d'investissement de plus faible ampleur dans l'amélioration des accès locaux. Deux options actuelles de financement de ces divers besoins se concentrent sur les seules politiques européennes, mais les investissements dans le capital physique non agricole et dans les infrastructures publiques ne peuvent pas se poursuivre sans des politiques nationales actives complémentant les efforts fournis au niveau européen, peut-être à travers des mécanismes de co-financement. Infrastruktur und Entwicklung des ländlichen Raums: Perspektiven aus den USA und der EU Bei der Entwicklung der Infrastruktur handelt es sich nach wie vor sowohl in den USA als auch in Europa um einen Eckpfeiler in der Politik zur Entwicklung des ländlichen Raums. Es ist offensichtlich, dass sich die Ziele bei der Entwicklung des ländlichen Raums unterscheiden, die Politikmaßnahmen ähneln sich jedoch. Die wirtschaftliche Begründung für die Entwicklung der Infrastruktur zielt auf die Effizienz und das Schaffen von Wettbewerbsvorteilen ab. Politikeingriffe sind gerechtfertigt, da die Bereitstellung von Infrastruktur in entlegenen, dünn besiedelten Gebieten höhere Kosten verursacht. Obgleich dieser Schwerpunkt der Politik den Erfolg noch nicht garantiert, verfügen die wirtschaftlich am weitesten entwickelten Regionen typischerweise über eine bessere physische Infrastruktur. In den USA muss sich die Politik an die Herausforderungen anpassen, welche eine in die Jahre gekommene Infrastruktur im ländlichen Raum und der demografische Wandel mit sich bringen, und wodurch neue Anforderungen an die soziale Infrastruktur, wie z.B. Wohnungsbau und Gesundheitseinrichtungen, gestellt werden. Bei der Finanzierung werden die Kommunen stärker in die Verantwortung genommen, und öffentlich-private Partnerschaften werden an Bedeutung gewinnen. In der EU besteht die größte Herausforderung darin, Ressourcen zu den neuen Mitgliedstaaten umzuverteilen, wo sowohl neue Großinvestitionen in die Transportnetzwerke als auch kleinere Investitionen zur Verbesserung des lokalen Zugangs dringend benötigt werden. Obwohl sich die beiden im Moment vorhandenen Optionen zur Finanzierung dieser vielfältigen Bedürfnisse ausschließlich auf europäische Politikmaßnahmen konzentrieren, können die Investitionen in außerlandwirtschaftliches physisches Kapital und in die öffentliche Infrastruktur nicht ohne wirksame Politikmaßnahmen auf nationaler Ebene (z.B. die Pflicht zur Kofinanzierung) als Ergänzung zu den Bemühungen auf europäischer Ebene aufrecht erhalten werden. [source] CETP inhibition in cardiovascular risk management: a critical appraisalEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2007R. P. F. Dullaart Abstract In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91,106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs. [source] Successful treatment of disseminated aspergillosis with the combination of voriconazole, caspofungin, granulocyte transfusions, and surgery followed by allogeneic blood stem cell transplantation in a patient with primary failure of an autologous stem cell graftEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005Robert Dinser Abstract:, The treatment of disseminated aspergillus infections in neutropenic patients remains a major challenge in spite of several new antifungal drugs. We report the case of a patient with multiple myeloma in prolonged neutropenia after primary failure of an autologous stem cell graft who developed invasive aspergillosis despite voriconazole monotherapy. He responded to a combination of voriconazole and caspofungin, supported by granulocyte transfusions and surgery. A subsequent allogeneic peripheral blood stem cell transplantation did not lead to recurring aspergillus infection. The patient is well and free of clinical disease with respect to the fungal infection and myeloma more than 18 months after the allogeneic transplantation. [source] Prevention of cancer through immunization: Prospects and challenges for the 21st centuryEUROPEAN JOURNAL OF IMMUNOLOGY, Issue S1 2007Abstract Persistent infection by several microbial agents is responsible for at least 15% of cancer globally, including most cancers of the liver, stomach, and cervix. The recent development of vaccines that can prevent infection and premalignant disease caused by human papillomaviruses (HPV), which cause virtually all cases of cervical cancer as well as some other cancers, has focused renewed attention on infection control as a means of reducing the global cancer burden. For vaccines to prevent cancer-causing infection with hepatitis C virus, Helicobacter pylori, or Epstein Barr virus, new vaccine technologies to induce more effective protective responses are required. For the two available cancer control vaccines, designed to prevent infection with HPV and hepatitis B virus, the major challenge is to promote effective vaccine deployment through education programs and increased affordability/accessibility for underserved populations, particularly in the developing world, where the cancer burden attributable to infection by these two viruses is greatest. [source] Quality of life in 1000 patients with early relapsing,remitting multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009N. Putzki Background and purpose:, To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing,remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment. Methods:, Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). Results:, A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58,1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51,0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75,0.78) vs. 0.75 (95%CI: 0.74,0.76) at baseline, 95%CI for difference: 0.01,0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. Conclusions:, Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. [source] Thermal Stability of W- xRe/TiC/SiC Systems,=,0, 5 and 25 at % Re) at High Temperature,ADVANCED ENGINEERING MATERIALS, Issue 5 2009Jerome Roger To ensure the integrity and sustainability of high-temperature applications, the development of protective materials is actually one of the major challenge in materials science. In our study, we examined the effect of a TiC film interlayered between W- xRe (x,=,0, 5 or 25 at % Re) and SiC. The protection given by TiC layer was considered in the 1573,1873,K temperature range and for TiC thicknesses up to about 100,,m. [source] Challenges and opportunities in soil organic matter researchEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2009R. Lal Summary Soil organic matter (SOM) can be a source or sink for atmospheric CO2 depending on land use, and management of soil, vegetation and water resources. SOM is a source of atmospheric CO2, with the use of extractive farming practices that lead to a negative nutrient balance and exacerbate soil degradation. The historic loss of C from the SOM pool between the 1850s and 2000 is estimated at 78 ± 12 Gt compared with the emission of 270 ± 30 Gt from fossil fuel combustion. Despite its numerous direct and ancillary benefits, enhancing the SOM pool is a major challenge, especially in impoverished and depleted soils in harsh tropical climates. In addition to biophysical factors, there are also numerous social, economic and political constraints that limit increase in SOM pools. Conversion of plough-tillage to no-till farming, an important practice to enhance the SOM pool, is constrained by the limited access to herbicides and seed drill, and the competing uses of crop residues. Yet, enhancing the SOM pool is essential to restoring degraded soils, advancing food security and improving the environment. Important subjects among researchable topics include: assessing the rate of SOM accretion for a wide range of land use and management practices with reference to a baseline; evaluating the importance of biochar; measuring and predicting SOM at landscape and extrapolation to regional scale; establishing relationships between SOM and soil quality and agronomic productivity; determining on- and off-site effects of crop residues removal for ethanol/biofuel production; determining the fate of C in SOM translocated by erosional processes; evaluating nutrient requirements for increasing SOM in croplands; validating predictive models in tropical environments; and developing methodology for trading C credits. [source] METAMODELS AND PHYLOGENETIC REPLICATION: A SYSTEMATIC APPROACH TO THE EVOLUTION OF DEVELOPMENTAL PATHWAYSEVOLUTION, Issue 11 2009Artyom Kopp Molecular genetic analysis of phenotypic variation has revealed many examples of evolutionary change in the developmental pathways that control plant and animal morphology. A major challenge is to integrate the information from diverse organisms and traits to understand the general patterns of developmental evolution. This integration can be facilitated by evolutionary metamodels,traits that have undergone multiple independent changes in different species and whose development is controlled by well-studied regulatory pathways. The metamodel approach provides the comparative equivalent of experimental replication, allowing us to test whether the evolution of each developmental pathway follows a consistent pattern, and whether different pathways are predisposed to different modes of evolution by their intrinsic organization. A review of several metamodels suggests that the structure of developmental pathways may bias the genetic basis of phenotypic evolution, and highlights phylogenetic replication as a value-added approach that produces deeper insights into the mechanisms of evolution than single-species analyses. [source] EMPIRICAL COMPARISON OF G MATRIX TEST STATISTICS: FINDING BIOLOGICALLY RELEVANT CHANGEEVOLUTION, Issue 10 2009Brittny Calsbeek A central assumption of quantitative genetic theory is that the breeder's equation (R=GP,1S) accurately predicts the evolutionary response to selection. Recent studies highlight the fact that the additive genetic variance,covariance matrix (G) may change over time, rendering the breeder's equation incapable of predicting evolutionary change over more than a few generations. Although some consensus on whether G changes over time has been reached, multiple, often-incompatible methods for comparing G matrices are currently used. A major challenge of G matrix comparison is determining the biological relevance of observed change. Here, we develop a "selection skewers"G matrix comparison statistic that uses the breeder's equation to compare the response to selection given two G matrices while holding selection intensity constant. We present a bootstrap algorithm that determines the significance of G matrix differences using the selection skewers method, random skewers, Mantel's and Bartlett's tests, and eigenanalysis. We then compare these methods by applying the bootstrap to a dataset of laboratory populations of Tribolium castaneum. We find that the results of matrix comparison statistics are inconsistent based on differing a priori goals of each test, and that the selection skewers method is useful for identifying biologically relevant G matrix differences. [source] NATURAL VARIATION FOR A HYBRID INCOMPATIBILITY BETWEEN TWO SPECIES OF MIMULUSEVOLUTION, Issue 1 2007Andrea L. Sweigart Understanding the process by which hybrid incompatibility alleles become established in natural populations remains a major challenge to evolutionary biology. Previously, we discovered a two-locus Dobzhansky,Muller incompatibility that causes severe hybrid male sterility between two inbred lines of the incompletely isolated wildflower species, Mimulus guttatus and M. nasutus. An interspecific cross between these two inbred lines revealed that the M. guttatus (IM62) allele at hybrid male sterility 1 (hms1) acts dominantly in combination with recessive M. nasutus (SF5) alleles at hybrid male sterility 2 (hms2) to cause nearly complete hybrid male sterility. In this report, we extend these genetic analyses to investigate intraspecific variation for the hms1,hms2 incompatibility in natural populations of M. nasutus and M. guttatus, performing a series of interspecific crosses between individuals collected from a variety of geographic locales. Our results suggest that hms2 incompatibility alleles are common and geographically widespread within M. nasutus, but absent or rare in M. guttatus. In contrast, the hms1 locus is polymorphic within M. guttatus and the incompatibility allele appears to be extremely geographically restricted. We found evidence for the presence of the hms1 incompatibility allele in only two M. guttatus populations that exist within a few kilometers of each other. The restricted distribution of the hms1 incompatibility allele might currently limit the potential for the hms1,hms2 incompatibility to act as a species barrier between sympatric populations of M. guttatus and M. nasutus. Extensive sampling within a single M. guttatus population revealed that the hms1 locus is polymorphic and that the incompatibility allele appears to segregate at intermediate frequency, a pattern that is consistent with either genetic drift or natural selection. [source] The dynamics of developmental system drift in the gene network underlying wing polyphenism in ants: a mathematical modelEVOLUTION AND DEVELOPMENT, Issue 3 2008Marcos Nahmad SUMMARY Understanding the complex interaction between genotype and phenotype is a major challenge of Evolutionary Developmental Biology. One important facet of this complex interaction has been called "Developmental System Drift" (DSD). DSD occurs when a similar phenotype, which is homologous across a group of related species, is produced by different genes or gene expression patterns in each of these related species. We constructed a mathematical model to explore the developmental and evolutionary dynamics of DSD in the gene network underlying wing polyphenism in ants. Wing polyphenism in ants is the ability of an embryo to develop into a winged queen or a wingless worker in response to an environmental cue. Although wing polyphenism is homologous across all ants, the gene network that underlies wing polyphenism has evolved. In winged ant castes, our simulations reproduced the conserved gene expression patterns observed in the network that controls wing development in holometabolous insects. In wingless ant castes, we simulated the suppression of wings by interrupting (up- or downregulating) the expression of genes in the network. Our simulations uncovered the existence of four groups of genes that have similar effects on target gene expression and growth. Although each group is comprised of genes occupying different positions in the network, their interruption produces vestigial discs that are similar in size and shape. The implications of our results for understanding the origin, evolution, and dissociation of the gene network underlying wing polyphenism in ants are discussed. [source] Seed-based systematic discovery of specific transcription factor target genesFEBS JOURNAL, Issue 12 2008Ralf Mrowka Reliable prediction of specific transcription factor target genes is a major challenge in systems biology and functional genomics. Current sequence-based methods yield many false predictions, due to the short and degenerated DNA-binding motifs. Here, we describe a new systematic genome-wide approach, the seed-distribution-distance method, that searches large-scale genome-wide expression data for genes that are similarly expressed as known targets. This method is used to identify genes that are likely targets, allowing sequence-based methods to focus on a subset of genes, giving rise to fewer false-positive predictions. We show by cross-validation that this method is robust in recovering specific target genes. Furthermore, this method identifies genes with typical functions and binding motifs of the seed. The method is illustrated by predicting novel targets of the transcription factor nuclear factor kappaB (NF-,B). Among the new targets is optineurin, which plays a key role in the pathogenesis of acquired blindness caused by adult-onset primary open-angle glaucoma. We show experimentally that the optineurin gene and other predicted genes are targets of NF-,B. Thus, our data provide a missing link in the signalling of NF-,B and the damping function of optineurin in signalling feedback of NF-,B. We present a robust and reliable method to enhance the genome-wide prediction of specific transcription factor target genes that exploits the vast amount of expression information available in public databases today. [source] The biology and ecology of lotic microturbellariansFRESHWATER BIOLOGY, Issue 1 2000Jurek Kolasa Summary 1More than 200 known species of Microturbellaria occur in running waters world-wide but discovery of many more is likely. Their population density varies greatly as a function of substratum, productivity, phenology and hydrology. The density may exceed 7 000 individuals m -2. The number of species in a single small sample may reach 20. 2Many species appear to have microhabitat or stream section specialisation but community patterns are obscured to a certain extent by common and eurytopic species. The specialisation is particularly evident in the smaller, lower-order streams. 3Some of this habitat specialisation is attributable to the ecological origin of species that may include terrestrial, underground, marine and lentic species pools. 4Feeding habits of Microturbellaria range from omnivory to specialised predation. 5Quantitative field studies require extraction and examination of live specimens from samples. Such samples pose transportation and storage problems and must be processed within hours of collection. 6Taxonomy is well resolved for the Northern Hemisphere but is likely to be a major challenge in other parts of the world. In any region, however, new species may demand caution while using current keys to their identification. [source] Management of type 2 diabetes: the GLP-1 pathwayFUTURE PRESCRIBER, Issue 3 2008Abd A Tahrani MMedSci Type 2 diabetes mellitus (T2DM) is a major challenge to healthcare systems around the world, with an estimated prevalence of 6% (246 million) in 2007 rising to 7.3% (380 million) in 2025 worldwide.1,5 In this article, the authors consider the significance of the GLP-1 path-way in the management of T2DM, and some of the advantages of incretin-based therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||