Getting the right words right

Oscar Wilde once complained that having spent an entire morning putting a comma into one of his poems, he spent the afternoon removing it. Peter Selgin calls this revisionitis: the inability of a writer to part with their work, the compulsion to go on fiddling and picking until there is nothing left to fret about. There can be real danger, Selgin warns, in fussing with things. The question then of how much to revise or how little to rewrite is one without certain answer and writers themselves hold differing views...

Two-scale computational modelling of unsaturated flow in soils exhibiting small scale heterogeneities

Unsaturated water flow in soil is commonly modelled using Richards’ equation, which requires the hydraulic properties of the soil (e.g., porosity, hydraulic conductivity, etc.) to be characterised. Naturally occurring soils, however, are heterogeneous in nature, that is, they are composed of a number of interwoven homogeneous soils each with their own set of hydraulic properties. When the length scale of these soil heterogeneities is small, numerical solution of Richards’ equation is computationally impractical due to the immense effort and refinement required to mesh the actual heterogeneous geometry. A classic way forward is to use a macroscopic model, where the heterogeneous medium is replaced with a fictitious homogeneous medium, which attempts to give the average flow behaviour at the macroscopic scale (i.e., at a scale much larger than the scale of the heterogeneities). Using the homogenisation theory, a macroscopic equation can be derived that takes the form of Richards’ equation with effective parameters. A disadvantage of the macroscopic approach, however, is that it fails in cases when the assumption of local equilibrium does not hold. This limitation has seen the introduction of two-scale models that include at each point in the macroscopic domain an additional flow equation at the scale of the heterogeneities (microscopic scale). This report outlines a well-known two-scale model and contributes to the literature a number of important advances in its numerical implementation. These include the use of an unstructured control volume finite element method and image-based meshing techniques, that allow for irregular micro-scale geometries to be treated, and the use of an exponential time integration scheme that permits both scales to be resolved simultaneously in a completely coupled manner. Numerical comparisons against a classical macroscopic model confirm that only the two-scale model correctly captures the important features of the flow for a range of parameter values.

The laws of the virtual worlds

What if you could check out of your world, and enter a place where the social environment was different, where real world laws didn't apply, and where the political system could be anything you wanted it to be? What if you could socialize there with family and friends, build your own palace, go skiing, and even hold down a job there? And what if there wasn't one alternate world, there were hundreds, and what if millions of people checked out of Earth and went there every day? Virtual worlds - online worlds where millions of people come to interact, play, and socialize - are a new type of social order. In this Article, we examine the implications of virtual worlds for our understanding of law, and demonstrate how law affects the interests of those within the world. After providing an extensive primer on virtual worlds, including their history and function, we examine two fundamental issues in detail. First, we focus on property, and ask whether it is possible to say that virtual world users have real world property interests in virtual objects. Adopting economic accounts that demonstrate the real world value of these objects and the exchange mechanisms for trading these objects, we show that, descriptively, these types of objects are indistinguishable from real world property interests. Further, the normative justifications for property interests in the real world apply - sometimes more strongly - in the virtual worlds. Second, we discuss whether avatars have enforceable legal and moral rights. Avatars, the user-controlled entities that interact with virtual worlds, are a persistent extension of their human users, and users identify with them so closely that the human-avatar being can be thought of as a cyborg. We examine the issue of cyborg rights within virtual worlds and whether they may have real world significance. The issues of virtual property and avatar rights constitute legal challenges for our online future. Though virtual worlds may be games now, they are rapidly becoming as significant as real-world places where people interact, shop, sell, and work. As society and law begin to develop within virtual worlds, we need to have a better understanding of the interaction of the laws of the virtual worlds with the law of this world.

Proteases and proteomics : cutting to the core of human skin pathologies

Preserving the integrity of the skin's outermost layer (the epidermis) is vital for humans to thrive in hostile surroundings. Covering the entire body, the epidermis forms a thin but impenetrable cellular cordon that repels external assaults and blocks escape of water and electrolytes from within. This structure exists in a perpetual state of regeneration where the production of new cellular subunits at the base of the epidermis is offset by the release of terminally differentiated corneocytes from the surface. It is becoming increasingly clear that proteases hold vital roles in assembling and maintaining the epidermal barrier. More than 30 proteases are expressed by keratinocytes or infiltrating immune cells and the activity of each must be maintained within narrow limits and confined to the correct time and place. Accordingly, over- or under-exertion of proteolytic activity is a common factor in a multitude of skin disorders that range in severity from relatively mild to life-threatening. This review explores the current state of knowledge on the involvement of proteases in skin diseases and the latest findings from proteomic and transcriptomic studies focused on uncovering novel (patho)physiological roles for these enzymes.

Baidu’s perfect paradox : free speech and the right to censor

China’s biggest search engine has a constitutional right to filter its search results, a US court found last month. But that’s just the start of the story. Eight New York-based pro-democracy activists sued Baidu Inc in 2011, seeking damages because Baidu prevents their work from showing up in search results. Baidu follows Chinese law that requires it to censor politically sensitive results. But in what the plaintiffs’ lawyer has dubbed a “perfect paradox”, US District Judge Jesse Furman has dismissed the challenge, explaining that to hold Baidu liable for its decisions to censor pro-democracy content would itself infringe the right to free speech.

Written in code : diversity and the new genetics

Modern genetic research holds out the promise of a bold new future in which humanity has identified and conquered the genetic roots of many diseases. Genetic science also promises to shed light on who we are, what it is that makes us tick, what it is that makes us the way we are — in short, what it is that makes us human. Yet while genetics are a potential saviour (saving us from disease), it also appears as a threat that at the extremes appears to be the stuff of our worst nightmares, such as the prospect, probably more imagined than real, of rows of cloned individuals. The new genetics hold out the promise that through genetics we will be able to determine what we are, a promise that is simultaneously appealing and terrifying. This chapter discusses the cloning of people and parts, the law’s response to cloning, genetics and diversity, a framework for law reform.

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

Background The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry. Objectives To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009. Selection criteria All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). Data collection and analysis Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one. Main results Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day). Authors' conclusions Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

Review : "Genetic Privacy: A challenge to Medico-Legal Norms" by Laurie, G

The discovery by Watson and Crick of the structure of DNA is one of the great scientific discoveries. In the period since that discovery new areas of genetic research have opened up which hold out the hope of developing treatments or cures for many illnesses and diseases. Yet with these discoveries have also come an array of ethical and legal dilemmas about the use of genetic information and concerns about the potential for those with genetic diseases or conditions to be stigmatised and discriminated against. The discussion about the developments in genetic science has become increasingly, a debate about the use of genetic information within our society. Graeme Laurie’s book, Genetic Privacy: A Challenge to Medico-Legal Norms, guides the reader through the complexities of these debates by considering what we mean by privacy and asking whether our existing concepts are adequate to meet the challenges posed by the new genetics.

Synthesis of MgB2 at low temperature and autogenous pressure

High quality, micron-sized interpenetrating grains of MgB2 with high density are produced at low temperatures (~420oC < T < ~500oC) under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5−15 hours. Optimum production of MgB2 with yields greater than 75% occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa with the reactor at ~500oC. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250oC for >20minutes prior to a hold at 500oC.

An outcome evaluation of the ‘Skipper’ designated driver program

The general aim of designated driver programs is to reduce the level of drink driving by encouraging potential drink drivers to travel with a driver who has abstained from (or at least limited) consuming alcohol. Designated driver programs appear to be quite widespread around the world, however a limited number have been subject to rigorous evaluation. This paper reports results from an outcome evaluation of a designated driver program called ‘Skipper’, which was trialled in a provincial city in Queensland, Australia. The outcome evaluation included surveys three weeks prior to (baseline), four months following (1st follow-up), and 16 months following (2nd follow-up) the commencement of the trial in both the ‘intervention area’ (baseline, n = 202; 1st follow-up, n = 211; 2nd follow-up, n = 200) and a ‘comparison area’(baseline, n = 203; 1st follow-up, n = 199; 2nd follow-up, n = 201); and a comparison of random breath testing and crash data before and after the trial. The survey results indicate that awareness of the program in the intervention area was quite high four months following its introduction and that this was maintained at 16 months. The results also suggest that the ‘Skipper’ program and the related publicity had positive impacts on behaviour with an increase in the proportion of people participating in designated driver as a passenger. It is less clear, however, whether the ‘Skipper’ program impacted on other behaviours of interest, such as drink driving or involvement in alcohol-related crashes. Suggestions for further research and program improvement are discussed as well as limitations of the research.

Cravings and Expectancies

Drug-dependent individuals commonly report craving, which is an urge to consume a substance to experience pleasure or provide relief. However, the motivation to use drugs is also influenced by the expectancies we hold about drug ingestion. Drug expectancies are among a range of internal and external cues that can elicit craving. Scientific advances in the neurobiology of reward have illuminated individual differences in the neurotransmitter systems involved in associative learning that underpin drug use motivation and expectancies. We have begun to elaborate the interrelationships of these constructs and mechanisms to inform new treatments that incorporate recent models of reward learning.

Epithelial mesenchymal transition traits in human breast cancer cell lines

Epithelial mesenchymal transition (EMT) has long been associated with breast cancer cell invasiveness and evidence of EMT processes in clinical samples is growing rapidly. Genome-wide transcriptional profiling of increasingly larger numbers of human breast cancer (HBC) cell lines have confirmed the existence of a subgroup of cell lines (termed Basal B/Mesenchymal) with enhanced invasive properties and a predominantly mesenchymal gene expression signature, distinct from subgroups with predominantly luminal (termed Luminal) or mixed basal/luminal (termed Basal A) features (Neve et al Cancer Cell 2006). Studies providing molecular and cellular analyses of EMT features in these cell lines are summarised, and the expression levels of EMT-associated factors in these cell lines are analysed. Recent clinical studies supporting the presence of EMT-like changes in vivo are summarised. Human breast cancer cell lines with mesenchymal properties continue to hold out the promise of directing us towards key mechanisms at play in the metastatic dissemination of breast cancer.

Comparison of accelerometer cut points for predicting activity intensity in youth

The absence of comparative validity studies has prevented researchers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents. PURPOSE This study aimed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure, measured by indirect calorimetry, as a criterion reference standard. METHODS A total of 206 participants between the ages of 5 and 15 yr completed 12 standardized activity trials. Trials consisted of sedentary activities (lying down, writing, computer game), lifestyle activities (sweeping, laundry, throw and catch, aerobics, basketball), and ambulatory activities (comfortable walk, brisk walk, brisk treadmill walk, running). During each trial, participants wore an ActiGraph GT1M, and VO 2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system. Physical activity intensity was estimated using five independently developed cut points: Freedson/Trost (FT), Puyau (PU), Treuth (TR), Mattocks (MT), and Evenson (EV). Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve (ROC-AUC). RESULTS Across all four intensity levels, the EV (κ = 0.68) and FT (κ = 0.66) cut points exhibited significantly better agreement than TR (κ = 0.62), MT (κ = 0.54), and PU (κ = 0.36). The EV and FT cut points exhibited significantly better classification accuracy for moderate-to vigorous-intensity physical activity (ROC-AUC = 0.90) than TR, PU, or MT cut points (ROC-AUC = 0.77-0.85). Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages. The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy (ROC-AUC = 0.90). CONCLUSIONS On the basis of these findings, we recommend that researchers use the EV ActiGraph cut points to estimate time spent in sedentary, light-, moderate-, and vigorous-intensity activity in children and adolescents. Copyright © 2011 by the American College of Sports Medicine.

Predictive validity of three ActiGraph energy expenditure equations for children

Purpose This Study evaluated the predictive validity of three previously published ActiGraph energy expenditure (EE) prediction equations developed for children and adolescents. Methods A total of 45 healthy children and adolescents (mean age: 13.7 +/- 2.6 yr) completed four 5-min activity trials (normal walking. brisk walking, easy running, and fast running) in ail indoor exercise facility. During each trial, participants were all ActiGraph accelerometer oil the right hip. EE was monitored breath by breath using the Cosmed K4b(2) portable indirect calorimetry system. Differences and associations between measured and predicted EE were assessed using dependent t-tests and Pearson correlations, respectively. Classification accuracy was assessed using percent agreement, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. Results None of the equations accurately predicted mean energy expenditure during each of the four activity trials. Each equation, however, accurately predicted mean EE in at least one activity trial. The Puyau equation accurately predicted EE during slow walking. The Trost equation accurately predicted EE during slow running. The Freedson equation accurately predicted EE during fast running. None of the three equations accurately predicted EE during brisk walking. The equations exhibited fair to excellent classification accuracy with respect to activity intensity. with the Trost equation exhibiting the highest classification accuracy and the Puyau equation exhibiting the lowest. Conclusions These data suggest that the three accelerometer prediction equations do not accurately predict EE on a minute-by-minute basis in children and adolescents during overground walking and running. The equations maybe, however, for estimating participation in moderate and vigorous activity.

Disparate companions : tissue engineering meets cancer research

Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue-specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit.