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Search Results: 1 - 10 of 2041 matches for " Will Steffen "
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The Anthropocene, global change and sleeping giants: where on Earth are we going?
Will Steffen
Carbon Balance and Management , 2006, DOI: 10.1186/1750-0680-1-3
Abstract: Although a very important exercise, this approach to defining dangerous climate change can itself be dangerous, in particular because it often ignores the systemic nature of the global environment. Feedbacks and nonlinearities are the rule, not the exception, in the functioning of the Earth System [2], and in this Anthropocene era, where human activities have become a global geophysical force in their own right, there is no doubt that surprises await those who apply linear logic to the climate problem. The carbon cycle is centrally involved in many of these feedbacks and nonlinearities.Here we briefly review several of the more important so-called "sleeping giants" in the carbon cycle, processes that have the potential to accelerate the rate of warming beyond that attributed to human emissions of greenhouse gases [3]. The first of these is based on the impact on soil respiration of rising temperature and changing soil moisture, an example of a response of ecosystem physiology to climate change. Although there is still debate about the magnitude of the increase in soil respiration with temperature, and whether there are compensating effects of enhanced plant growth due to mobilisation of nitrogen in the process, the general consensus is that increasing temperature will cause an increase in the emission of CO2 from soil carbon [4].A second "sleeping giant" is the increase in disturbance in terrestrial ecosystems, often associated with pulses of carbon to the atmosphere. The most notable of these are wildfires and pest outbreaks, both sensitive to both warming and changes in the moisture regime. Although these are natural phenomena in the dynamics of terrestrial ecosystems, an increase in the frequency or extent of these disturbances results in a net loss of carbon to the atmosphere. Observations of the large areas of boreal forest in the northern high latitudes suggest that over the past couple of decades, these forests have experienced enhanced rates and/or areas of
Future direction of pathogenesis and treatment for rheumatic disorders
Steffen Gay
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3556
Abstract: Millions of patients have tremendously benefitted. However, we cannot cure these diseases yet and have to search for additional therapeutic targets.Since it was shown that synovial fibroblasts (SF) are not only effector cells responding to inflammatory stimuli, but appear endogenously activated and potentially involved into spreading the disease [1], we searched for the epigenetic modifications leading to the activated phenotype of these cells.Epigenetics in its scientific definition "is the study of all heritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA", but might be considered in simpler terms as the regulation of gene expression.Epigenetic modifications include:Acetylation,Methylation,Phosphorylation,Sumoylation,miRs or microRNAs.Our laboratory is studying these processes and we have found that RASF reside in a hyperacetylated synovial tissue and appear hypomethylated [2]. Hypomethylation leads to the activated phenotype of RASF which is characterized by the production of matrix-degrading enzymes and of potent chemokines induced by Toll-like receptor signalling. Current strategies are designed to methylate these cells to deactivate and "normalise" them again.miRs are about 20 nucleotide long smallRNAs acting to destroy specific mRNA.In the race to identify specific miRs as novel targets we have identified for example, that interleukin-6 modulates the expression of the Bone Morphogenic Protein Receptor Type II through a novel STAT3microRNA cluster 17/92 pathway, which helps to explain the loss of the BMPR2 in the vascular cells in pulmonary hypertension [3]. Moreover, miR-203 is regulating the production of IL-6 [4].Most interestingly, epigenetic therapy is also on the horizon [5].
Sustainable Construction for Urban Infill Development Using Engineered Massive Wood Panel Systems
Steffen Lehmann
Sustainability , 2012, DOI: 10.3390/su4102707
Abstract: Prefabricated engineered solid wood panel construction systems can sequester and store CO2. Modular cross-laminated timber (CLT, also called cross-lam) panels form the basis of low-carbon, engineered construction systems using solid wood panels that can be used to build residential infill developments of 10 storeys or higher. Multi-apartment buildings of 4 to 10 storeys constructed entirely in timber, such as recently in Europe, are innovative, but their social and cultural acceptance in Australia and North America is at this stage still uncertain. Future commercial utilisation is only possible if there is a user acceptance. The author is part of a research team that aims to study two problems: first models of urban infill; then focus on how the use of the CLT systems can play an important role in facilitating a more livable city with better models of infill housing. Wood is an important contemporary building resource due to its low embodied energy and unique attributes. The potential of prefabricated engineered solid wood panel systems, such as CLT, as a sustainable building material and system is only just being realised around the globe. Since timber is one of the few materials that has the capacity to store carbon in large quantities over a long period of time, solid wood panel construction offers the opportunity of carbon engineering, to turn buildings into ‘carbon sinks’. Thus some of the historically negative environmental impact of urban development and construction can be turned around with CLT construction on brownfield sites.
Optimizing Urban Material Flows and Waste Streams in Urban Development through Principles of Zero Waste and Sustainable Consumption
Steffen Lehmann
Sustainability , 2011, DOI: 10.3390/su3010155
Abstract: Beyond energy efficiency, there are now urgent challenges around the supply of resources, materials, energy, food and water. After debating energy efficiency for the last decade, the focus has shifted to include further resources and material efficiency. In this context, urban farming has emerged as a valid urban design strategy, where food is produced and consumed locally within city boundaries, turning disused sites and underutilized public space into productive urban landscapes and community gardens. Furthermore, such agricultural activities allow for effective composting of organic waste, returning nutrients to the soil and improving biodiversity in the urban environment. Urban farming and resource recovery will help to feed the 9 billion by 2050 (predicted population growth, UN-Habitat forecast 2009). This paper reports on best practice of urban design principles in regard to materials flow, material recovery, adaptive re-use of entire building elements and components (‘design for disassembly’; prefabrication of modular building components), and other relevant strategies to implement zero waste by avoiding waste creation, reducing wasteful consumption and changing behaviour in the design and construction sectors. The paper touches on two important issues in regard to the rapid depletion of the world’s natural resources: the built environment and the education of architects and designers (both topics of further research). The construction and demolition (C&D) sector: Prefabricated multi-story buildings for inner-city living can set new benchmarks for minimizing construction wastage and for modular on-site assembly. Today, the C&D sector is one of the main producers of waste; it does not engage enough with waste minimization, waste avoidance and recycling. Education and research: It’s still unclear how best to introduce a holistic understanding of these challenges and to better teach practical and affordable solutions to architects, urban designers, industrial designers, and so on. How must urban development and construction change and evolve to automatically embed sustainability in the way we design, build, operate, maintain and renew/recycle cities? One of the findings of this paper is that embedding zero-waste requires strong industry leadership, new policies and effective education curricula, as well as raising awareness (through research and education) and refocusing research agendas to bring about attitudinal change and the reduction of wasteful consumption.
Coherence of evidence from systematic reviews as a basis for evidence strength - a case study in support of an epistemological proposition
Steffen Mickenautsch
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-26
Abstract: A case study including seven systematic reviews is presented with the objective of refuting radical philosophical scepticism towards the belief that glass-ionomer cements (GIC) are beneficial in tooth caries therapy. The case study illustrates how principles of logical and empirical coherence may be applied as evidence in support of specific beliefs in healthcare.The results show that radical scepticism may epistemologically be refuted on the basis of logical and empirical coherence. For success, several systematic reviews covering interconnected beliefs are needed. In praxis, these systematic reviews would also need to be of high quality and its conclusions based on reviewed high quality trials.A refutation of radical philosophical scepticism to clinical evidence may be achieved, if and only if such evidence is based on the logical and empirical coherence of multiple systematic review results. Practical application also requires focus on the quality of the systematic reviews and reviewed trials.Epistemology is described as the branch of philosophy that concerns itself with questions regarding human knowledge [1]. One particular epistemological question relates to the Object - Subject distinction and asks whether the objective world is subjectively knowable at all. It has been proposed that the real (objective) world and our (subjective) perception of the real world are not the same. Descartes (1641) argued that all that we can know of the real world is tainted by our senses and abilities of understanding [2]. Kant (1998 [1781]) distinguished between the unknowable Ding an sich (German: The thing in itself) and the knowable Erscheinung (German: Phenomenon) [3]. Postmodernism contends that the notion of reality is an illusion [4]. Quine (1964) described physical objects as mere cultural posits [5], and cognitive psychology and neuroscience have presented evidence that sense experience, the 'bedrock of empirical knowledge', is actively edited by human perception [4].
Systematic reviews, systematic error and the acquisition of clinical knowledge
Steffen Mickenautsch
BMC Medical Research Methodology , 2010, DOI: 10.1186/1471-2288-10-53
Abstract: The various types of clinical knowledge sources are categorised on the basis of Kant's categories of knowledge acquisition, as being either 'analytic' or 'synthetic'. It is shown that these categories do not act in opposition but rather, depend upon each other. The unity of analysis and synthesis in knowledge acquisition is demonstrated during the process of systematic reviewing of clinical trials. Systematic reviews constitute comprehensive synthesis of clinical knowledge but depend upon plausible, analytical hypothesis development for the trials reviewed. The dangers of systematic error regarding the internal validity of acquired knowledge are highlighted on the basis of empirical evidence. It has been shown that the systematic review process reduces systematic error, thus ensuring high internal validity. It is argued that this process does not exclude other types of knowledge sources. Instead, amongst these other types it functions as an integrated element during the acquisition of clinical knowledge.The acquisition of clinical knowledge is based on interaction between analysis and synthesis. Systematic reviews provide the highest form of synthetic knowledge acquisition in terms of achieving internal validity of results. In that capacity it informs the analytic knowledge of the clinician but does not replace it.Systematic reviews, in healthcare, have been described as providing objective overviews of all the evidence currently available on a particular topic of interest [1]. Such overviews cover clinical trials in order to establish where effects of healthcare are consistent and where they may vary. This is achieved through the use of explicit, systematic methods aimed at limiting systematic error (bias) and reducing the chance of effect [2]. Systematic reviews have been recommended as providing the best source of evidence to guide clinical decisions [3,4] and healthcare policy [5], and they receive twice as many citations as non-systematic reviews in peer-review
Research gaps identified during systematic reviews of clinical trials: glass-ionomer cements
Steffen Mickenautsch
BMC Oral Health , 2012, DOI: 10.1186/1472-6831-12-18
Abstract: Information concerning research gaps in trial precision was extracted, following a framework that included classification of the research gap reasons: ‘imprecision of information (results)’, ‘biased information’, ‘inconsistency or unknown consistency’ and ‘not the right information’, as well as research gap characterization using PICOS elements: population (P), intervention (I), comparison (C), outcomes (O) and setting (S). Internal trial validity assessment was based on the understanding that successful control for systematic error cannot be assured on the basis of inclusion of adequate methods alone, but also requires empirical evidence about whether such attempt was successful.A comprehensive and interconnected coverage of GIC-related clinical topics was established. The most common reasons found for gaps in trial precision were lack of sufficient trials and lack of sufficient large sample size. Only a few research gaps were ascribed to ‘Lack of information’ caused by focus on mainly surrogate trial outcomes. According to the chosen assessment criteria, a lack of adequate randomisation, allocation concealment and blinding/masking in trials covering all reviewed GIC topics was noted (selection- and detection/performance bias risk). Trial results appear to be less affected by loss-to-follow-up (attrition bias risk).This audit represents an adjunct of the systematic review articles it has covered. Its results do not change the systematic review’s conclusions but highlight existing research gaps concerning the precision and internal validity of reviewed trials in detail. These gaps should be addressed in future GIC-related clinical research.
Galileo and Huygens on free fall: Mathematical and methodological differences
Dynamis , 2008, DOI: 10.4321/S0211-95362008000100011
Abstract: in this essay, i will scrutinize the differences between galileo's and huygens's demonstrations of free fall, which can be found respectively in the discorsi and the horologium, from a mathematical, representational and methodological perspective. i argue that more can be learnt from such an analysis than the thesis that huygens re-styled galilean mechanics which is a communis opinio. i shall argue that the differences in their approach on free fall highlight a significantly different mathematical and methodological outlook.
A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors
Steffen Eikenberry
Theoretical Biology and Medical Modelling , 2009, DOI: 10.1186/1742-4682-6-16
Abstract: A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration.The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy.Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.Doxorubicin (adriamycin) is a first line anti-neoplastic agent used against a number of solid tumors, leukemias, and lymphomas [1]. There are many proposed mechanisms by which doxorubicin (DOX) may induce cellular death, including DNA synthesis inhibition, DNA alkylation, and free radical generation. It is known to bind to nuclear DNA and inhibit topoisomera
As esferas seculares e religiosas na sociedade portuguesa
Análise Social , 2010,
Abstract: this article seeks to redesign the borders and the overlaps between the secular and religious spheres of portuguese society. in methodological terms, i propose an historical-sociological approach, comparing especially the reconfigurations of portuguese catholicism under different socio-cultural conditions during the 19th and 20th centuries. on the basis of this analysis, i revisit the dual perspective of being either religious or secular, and try to recognize the simultaneous existence and the link between the religious and secular spheres in a modern european society.
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