Distribution-based bisimulation for labelled Markov processes

In this paper we propose a (sub)distribution-based bisimulation for labelled Markov processes and compare it with earlier definitions of state and event bisimulation, which both only compare states. In contrast to those state-based bisimulations, our distribution bisimulation is weaker, but corresponds more closely to linear properties. We construct a logic and a metric to describe our distribution bisimulation and discuss linearity, continuity and compositional properties.Comment: Accepted by FORMATS 201

Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance

Dolutegravir (DTG), a second-generation integrase strand-transfer inhibitor (INSTI), is equivalent or superior to current non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and first-generation INSTI-based antiretroviral regimens (ARVs). It has the potential to make big improvements in HIV control globally and within patients. This is perhaps the most “precious” HIV drug available. The integrase mutation R263K has been observed in tissue culture experiments and in patients treated with dolutegravir monotherapy in clinical trials. Globally, adherence and monitoring may be less than optimal and therefore DTG resistance more common. This is particularly important in low–middle-income countries, where patients may remain on failing regimens for longer periods of time and accumulate drug resistance. Data on this mutation in non–subtype B infections do not exist. We describe the first report of the R263K integrase mutation in a dolutegravir-exposed subtype D–infected individual with vertically acquired HIV. We have used deep sequencing of longitudinal samples to highlight the change in resistance over time while on a failing regimen. The case highlights that poorly adherent patients should not be offered dolutegravir even as part of a combination regimen and that protease inhibitors should be used preferentially

Struggles at the summits:Discourse coalitions, field boundaries, and the shifting role of business in sustainable development

This research explores the field dynamics that facilitated the emergence of a dominant understanding of business’ role in sustainable development (SD). Based on a study of the U.N. Earth Summits, we examine how actors meet every decade to battle for definitional control of what SD means for business, and what business means for SD. Through a discourse analysis of texts from business, policy, and civil society actors during each Summit, we illustrate how an ensuing discursive struggle shifts the role of business in SD from being largely undefined in 1992, to being considered an SD partner in 2002, and finally to becoming a driver of SD by 2012. We contend that these shifts occurred largely due to two field dynamics: (a) rearranging of field boundaries and (2) forming of a discourse coalition. Accordingly, our study highlights how disparate actors coalesce around a shared-meaning system and collectively shape the role of business role in SD. However, we argue that despite the allure of a unified meaning-making process between once antagonistic actors, business–SD relations are underpinned by politicized interaction where certain actors come to dominate, and, in doing so, marginalize others

Drilling their own graves:How the European oil and gas supermajors avoid sustainability tensions through mythmaking

This study explores how paradoxical tensions between economic growth and environmental protection are avoided through organizational mythmaking. By examining the European oil and gas supermajors’ ‘‘CEOspeak’’ about climate change, we show how mythmaking facilitates the disregarding, diverting, and/or displacing of sustainability tensions. In doing so, our findings further illustrate how certain defensive responses are employed: (1) regression, or retreating to the comforts of past familiarities, (2) fantasy, or escaping the harsh reality that fossil fuels and climate change are indeed irreconcilable, and (3) projecting, or shifting blame to external actors for failing to address climate change. By highlighting the discursive effects of enacting these responses, we illustrate how the European oil and gas supermajors self-determine their inability to substantively address the complexities of climate change. We thus argue that defensive responses are not merely a form of mismanagement as the paradox and corporate sustainability literature commonly suggests, but a strategic resource that poses serious ethical concerns given the imminent danger of issues such as climate change

Dietary fruits and vegetables and cardiovascular diseases risk

Diet is likely to be an important determinant of cardiovascular disease (CVD) risk. In this article, we will review the evidence linking the consumption of fruit and vegetables and CVD risk. The initial evidence that fruit and vegetable consumption has a protective effect against CVD came from observational studies. However, uncertainty remains about the magnitude of the benefit of fruit and vegetable intake on the occurrence of CVD and whether the optimal intake is five portions or greater. Results from randomized controlled trials do not show conclusively that fruit and vegetable intake protects against CVD, in part because the dietary interventions have been of limited intensity to enable optimal analysis of their putative effects. The protective mechanisms of fruit and vegetables may not only include some of the known bioactive nutrient effects dependent on their antioxidant, anti-inflammatory, and electrolyte properties, but also include their functional properties, such as low glycemic load and energy density. Taken together, the totality of the evidence accumulated so far does appear to support the notion that increased intake of fruits and vegetables may reduce cardiovascular risk. It is clear that fruit and vegetables should be eaten as part of a balanced diet, as a source of vitamins, fiber, minerals, and phytochemicals. The evidence now suggests that a complicated set of several nutrients may interact with genetic factors to influence CVD risk. Therefore, it may be more important to focus on whole foods and dietary patterns rather than individual nutrients to successfully impact on CVD risk reduction. A clearer understanding of the relationship between fruit and vegetable intake and cardiovascular risk would provide health professionals with significant information in terms of public health and clinical practice

Development and optimization of quantitative PCR for the diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid

Background: The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. Culture and histopathological examination of bronchoalveolar lavage (BAL) fluid are useful but have suboptimal sensitivity and in the case of culture may require several days for fungal growth to be evident. Detection of Aspergillus DNA in BAL fluid by quantitative PCR (qPCR) offers the potential for earlier diagnosis and higher sensitivity. It is important to adopt quality control measures in PCR assays to address false positives and negatives which can hinder accurate evaluation of diagnostic performance. Methods: BAL fluid from 94 episodes of pneumonia in 81 patients was analyzed. Thirteen episodes were categorized as proven or probable IPA using Mycoses Study Group criteria. The pellet and the supernatant fractions of the BAL were separately assayed. A successful extraction was confirmed with a human 18S rRNA gene qPCR. Inhibition in each qPCR was measured using an exogenous DNA based internal amplification control (IAC). The presence of DNA from pathogens in the Aspergillus genus was detected using qPCR targeting fungal 18S rRNA gene. Results: Human 18S rRNA gene qPCR confirmed successful DNA extraction of all samples. IAC detected some degree of initial inhibition in 11 samples. When culture was used to diagnose IPA, the sensitivity and specificity were 84.5% and 100% respectively. Receiver-operating characteristic analysis of qPCR showed that a cutoff of 13 fg of Aspergillus genomic DNA generated a sensitivity, specificity, positive and negative predictive value of 77%, 88%, 50%, 96% respectively. BAL pellet and supernatant analyzed together resulted in sensitivity and specificity similar to BAL pellet alone. Some patients did not meet standard criteria for IPA, but had consistently high levels of Aspergillus DNA in BAL fluid by qPCR. Conclusion: The Aspergillus qPCR assay detected Aspergillus DNA in 76.9% of subjects with proven or probable IPA when the concentrated BAL fluid pellet fraction was used for diagnosis. There was no benefit from analyzing the BAL supernatant fraction. Use of both extraction and amplification controls provided optimal quality control for interpreting qPCR results and therefore may increase our understanding of the true potential of qPCR for the diagnosis of IPA.Supported by NIH grant R01 AI054703 from the National Institute of Allergy and Infectious Diseases

Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

Background: State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings: The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance: The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution fo