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Bacteriophages were first identified in 1915 and were used as antimicrobial agents from 1919 onwards. Despite apparent successes and widespread application, early users did not understand the nature of these agents and their efficacy remained controversial. As a result, they were replaced in the west by chemical antibiotics once these became available. However, bacteriophages remained a common therapeutic approach in parts of Eastern Europe where they are still in use. Increasing levels of antibiotic-resistant bacterial infections are now driving demand for novel therapeutic approaches. In cases where antibiotic options are limited or nonexistent, the pressure for new agents is greatest. One of the most prominent areas of concern is multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa is a prominent member of this class and is the cause of damaging infections that can be resistant to successful treatment with conventional antibiotics. At the same time, it exhibits a number of properties that make it a suitable target for bacteriophage-based approaches, including growth in biofilms that can hydrolyse following phage infection. Pseudomonas aeruginosa provides a striking example of an infection where clinical need and the availability of a practical therapy coincide. [ABSTRACT FROM AUTHOR]

The empirical models commonly used for probabilistic life prediction do not provide adequate treatment of the physical parameters that characterize fatigue damage development. For these models, probabilistic treatment is limited to statistical analysis of strain-life regression fit parameters. In this paper a model is proposed for life prediction that is based on separate nucleation and growth phases of total fatigue life. The model was calibrated using existing smooth specimen strain-life data, and it has been validated for other geometries. Crack nucleation scatter is estimated based on the variability associated with smooth specimen and fatigue crack growth data, including the influences of correlation among crack nucleation and growth phases. The influences of crack nucleation and growth variability on life and probability of fracture are illustrated for a representative gas turbine engine disk geometry. [ABSTRACT FROM AUTHOR]

This paper summarizes the development of a probabilistic micromechanical code for treating fatigue life variability resulting from material variations. Dubbed MICROFAVA (micromechanical fatigue variability), the code is based on a set of physics-based fatigue models that predict fatigue crack initiation life, fatigue crack growth life, fatigue limit, fatigue crack growth threshold, crack size at initiation, and fracture toughness. Using microstructure information as material input, the code is capable of predicting the average behavior and the confidence limits of the crack initiation and crack growth lives of structural alloys under LCF or HCF loading. This paper presents a summary of the development of the code and highlights applications of the model to predicting the effects of microstructure on the fatigue crack growth response and life variability of the α+ β Ti-alloy Ti-6Al-4V. [ABSTRACT FROM AUTHOR]

Endospore-forming bacteria, Paenibacillus spp., have recently been isolated in association with insect pathogenic netnatodes Heterorhabditis spp. Sporangia adhere to nematode infective juveniles (J3) and are carried with them into insects. Paenibacillus proliferates in the killed insect along with Heterorhabditis and its obligate bacterial symbiont, Photorhabdus, despite the antibiotic production of the latter. Nematode infective juveniles leave the insect cadaver with Paenibacillus sporangia attached. The specificity of the relationship between Paenibacillus and Heterorhabditis was investigated. Sporangia of nematode-associated Paenibacillus adhered to infective juveniles (but not other stages) of all Heterorhabditis species tested, and lo infective juveniles of vertebrate parasitic Strongylida species, but not to a variety of other soil nematodes tested. Paenibacillus species that were not isolated from nematodes, but were phylogenetically close to the nematode-associated strains, did not adhere to Heterorhabditis, and they were also sensitive to Photorhabdus antibiotics in vitro, whereas the nematode-associated strains were not. Unusual longevity of the sporangium and resistance to Photorhabdus antibiotics may represent specific adaptations of the nematode-associated Paenibacillus strains to allow them to coexist with and be transported by Heterorhabditis. Adaptation to specific Heterorhabditis- Photorhabdus strains is evident among the three nematode- associated Paenibacillus strains (each from a different nematode strain). Paenibacillus NEM1a and NEM3 each developed best in cadavers with the nematode from which it was isolated and not at all with the nematode associate of the other strain. Differences between nematode-associated Paenibacillus strains in cross-compatibility with the various Heterorhabditis strains in cadavers could not be explained by differential sensitivity to antibiotics produced by the nematodes' Photorhabdus symbionts in vitro. [ABSTRACT FROM AUTHOR]

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in many countries is increasing and, in hospitals in some areas, more than half of all S. aureus disease isolates are MRSA. MRSA strains are becoming increasingly multiresistant, and have recently developed resistance to vancomycin, used successfully to treat MRSA for more than 30 years. This review summarises recent studies that have elucidated the evolutionary history of MRSA. The first MRSA isolate evolved from a sensitive, epidemic strain prevalent in Europe, and its progeny—the first MRSA clone—quickly spread to other continents. Analyses of epidemic MRSA isolates from hospitals in different countries by molecular methods, including multilocus sequence typing (MLST) and DNA microarray analysis, reveal that MRSA strains have evolved separately within five distinct epidemic, sensitive lineages. However, resistance has been transferred to S. aureus on many more than five occasions, as some lineages have acquired different structural types of the element carrying the methicillin resistance gene. The emergence of MRSA as a community pathogen has been noted in several countries, and MLST and SCC mec typing have been used to demonstrate that community-acquired MRSA strains are typically related only distantly to hospital MRSA strains, and thus represent novel acquisitions of SCC mec. [ABSTRACT FROM AUTHOR]

Presents the probabilistic fatigue analysis methodology developed for DARWIN, a computer program. Probabilistic life prediction methodology; Computational methods for reliability-based life prediction under inspection; Numerical illustration of probabilistic computational methods.

Presents an abstract of the study "Multilocus Sequence Typing and the Evolution of Methicillin-Resistant Staphylococcus aureus," by D.A. Robinson and M.C. Enright from a 2004 issue of "Clinical Microbiology and Infection."

Biofilms are major causes of impairment of wound healing and patient morbidity. One of the most common and aggressive wound pathogens is Staphylococcus aureus, displaying a large repertoire of virulence factors and commonly reduced susceptibility to antibiotics, such as the spread of methicillin-resistant S. aureus (MRSA). Bacteriophages are obligate parasites of bacteria. They multiply intracellularly and lyse their bacterial host, releasing their progeny. We isolated a novel phage, DRA88, which has a broad host range among S. aureus bacteria. Morphologically, the phage belongs to the Myoviridae family and comprises a large double-stranded DNA (dsDNA) genome of 141,907 bp. DRA88 was mixed with phage K to produce a high-titer mixture that showed strong lytic activity against a wide range of S. aureus isolates, including representatives of the major international MRSA clones and coagulase-negative Staphylococcus. Its efficacy was assessed both in planktonic cultures and when treating established biofilms produced by three different biofilm-producing S. aureus isolates. A significant reduction of biofilm biomass over 48 h of treatment was recorded in all cases. The phage mixture may form the basis of an effective treatment for infections caused by S. aureus biofilms. [ABSTRACT FROM AUTHOR]

Staphylococcal chromosome cassette mec (SCC mec) elements within major lineages of healthcare- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) clones were characterised using intra-SCC mec multilocus sequencing. A strong correlation was observed between sequence- and PCR-based typing methods (p <0.001). However, phylogenetic analysis of the SCC mec locus using concatenated sequences evidenced few recombination events. Sequence type (ST)-SCC mec1 was found in SCC mec elements types I and IV, suggesting the evolution of an SCC mecI element into an SCC mecIV element. This coincided with the spread of the clone harbouring this SCC mec element into the community. No correlation was observed between ST-SCC mec lineage and MRSA lineage, confirming multiple acquisitions of SCC mec by S. aureus. This was exemplified by the SCC mecIV ST-SCC mec10 element, which was detected in all of the clonal complexes examined, including healthcare- and community-associated MRSA. The acquisition of this SCC mec element was five- to ten-fold more common than that of others. Models of MRSA clone evolution suggest that this SCC mec was first found in the paediatric clone. [ABSTRACT FROM AUTHOR]

This paper summarizes recent enhancements to a probabilistic damage tolerance software code, DARWIlV™, that can be used for design certification of aircraft jet engine titanium disks/rotors that may contain melt-related anomalies. Evaluations of DARWIN™ by engine manufacturers are also discussed, including comparisons with existing codes for accuracy and time efficiency. In addition, relevant test results, including various fatigue tests on material containing melt-related anomalies, are summarized. [ABSTRACT FROM AUTHOR]

Despite its importance as a human pathogen, information on population structure and global epidemiology of Staphylococcus epidermidis is scarce and the relative importance of the mechanisms contributing to clonal diversification is unknown. In this study, we addressed these issues by analyzing a representative collection of S. epidermidis isolates from diverse geographic and clinical origins using multilocus sequence typing (MLST). Additionally, we characterized the mobile element (SCCmec) carrying the genetic determinant of methicillin resistance. The 217 S. epidermidis isolates from our collection were split by MLST into 74 types, suggesting a high level of genetic diversity. Analysis of MLST data using the eBURST algorithm revealed the existence of nine epidemic clonal lineages that were disseminated worldwide. One single clonal lineage (clonal complex 2) comprised 74% of the isolates, whereas the remaining isolates were clustered into 8 minor clonal lineages and 13 singletons. According to our evolutionary model, SCCmec was acquired at least 56 times by S. epidermidis. Although geographic dissemination of S. epidermidis strains and the value of the index of association between the alleles, 0.2898 (P < 0.05), support the clonality of S. epidermidis species, examination of the sequence changes at MLST loci during clonal diversification showed that recombination gives rise to new alleles approximately twice as frequently as point mutations. We suggest that S. epidermidis has a population with an epidemic structure, in which nine clones have emerged upon a recombining background and evolved quickly through frequent transfer of genetic mobile elements, including SCCmec. [ABSTRACT FROM AUTHOR]