Modeling Concurrency in Parallel Debugging

We propose a description language, Data Path Expressions (DPEs), for modeling the behavior of parallel programs. We have designed DPEs as a high-level debugging language, where the debugging paradigm is for the programmer to describe the expected program behavior and for the debugger to compare the actual program behavior during execution to detect program errors. We classify DPEs into five subclasses according to syntactic criteria, and characterize their semantics in terms of a hierarchy of extended Petri Net models. The characterization demonstrates the power of DPEs for modeling (true) concurrency. We also present predecessor automata as a mechanism for implementing the third subclass of DPEs, which expresses bounded parallelism. Predecessor automata extend finite state automata to recognize or generate partial ordering graphs as well as strings, and provide efficient event recognizers for parallel debugging. We briefly describe the application of DPEs race conditions, deadlock and starvation

Morbidity from in-hospital complications is greater than treatment failure in patients with Staphylococcus aureus bacteraemia

Background: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. Methods: Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. Results: Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. Conclusions: This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications

Prediction Model to Identify Patients at Risk of 30-Day Treatment Failure in Patients With Staphylococcus aureus Bacteremia

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Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen

Transformational capacity and the influence of place and identity

Climate change is altering the productivity of natural resources with far-reaching implications for those who depend on them. Resource-dependent industries and communities need the capacity to adapt to a range of climate risks if they are to remain viable. In some instances, the scale and nature of the likely impacts means that transformations of function or structure will be required. Transformations represent a switch to a distinct new system where a different suite of factors become important in the design and implementation of response strategies. There is a critical gap in knowledge on understanding transformational capacity and its influences. On the basis of current knowledge on adaptive capacity we propose four foundations for measuring transformational capacity: (1)how risks and uncertainty are managed, (2)the extent of skills in planning, learning and reorganizing, (3)the level of financial and psychological flexibility to undertake change and (4)the willingness to undertake change. We test the influence of place attachment and occupational identity on transformational capacity using the Australian peanut industry, which is presently assessing significant structural change in response to predicted climatic changes. Survey data from 88% of peanut farmers in Queensland show a strong negative correlation between transformational capacity and both place attachment and occupational attachment, suggesting that whilst these factors may be important positive influences on the capacity to adapt to incremental change, they act as barriers to transformational change

Landholder Typologies Used in the Development of Natural Resource Management Programs in Australia - A Review

This article reviews the literature on the identification of landholder typologies that can be used to assist the design and delivery of natural resource management (NRM) programs. Australian researchers have developed typologies of landholders based on a variety of criteria. The rationale for developing landholder typologies is first discussed before reviewing the various approaches that have been used by Australian researchers and comparing their findings. The methods employed have differed according to the theories used to guide the research and the 'clients' or 'sponsors' of the research. The landholder types they describe, however, have a number of similarities. These similarities suggest that the studies have identified the same fundamental divisions in the rural community, and that it may be possible to integrate landholder typologies for a variety of NRM and non-NRM applications. It is concluded that further research could usefully investigate whether concepts of social class or sub-cultures may be appropriate to define and describe the variations in landholder types

Genomic insights to control the emergence of vancomycin-resistant enterococci.

UNLABELLED: Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm. IMPORTANCE: Enterococcus faecium is an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in hospitals globally, yet in many institutions around the world, vancomycin-resistant E. faecium (VREfm) infections continue to rise. The new findings from this study help explain the failures of our current approaches to controlling vanB VREfm in health care institutions. Given the importance of this bacterium as a cause of hospital-acquired infections and the difficulties faced by infection control units in trying to prevent colonization in their institutions, the novel findings from this study provide evidence that a new approach to controlling VREfm in hospitals is required. In particular, more attention should be given to understanding the epidemiology of hospital-adapted vancomycin-susceptible E. faecium, and patients at higher risk for de novo generation of VREfm need to be identified and optimally managed

Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge