AMS-100: The Next Generation Magnetic Spectrometer in Space - An International Science Platform for Physics and Astrophysics at Lagrange Point 2.

The next generation magnetic spectrometer in space, AMS-100, is designed to have a geometrical acceptance of 100 m2 sr and to be operated for at least ten years at the Sun-Earth Lagrange Point 2. Compared to existing experiments, it will improve the sensitivity for the observation of new phenomena in cosmic rays, and in particular in cosmic antimatter, by at least a factor of 1000. The magnet design is based on high temperature superconductor tapes, which allow the construction of a thin solenoid with a homogeneous magnetic field of 1 Tesla inside. The inner volume is instrumented with a silicon tracker reaching a maximum detectable rigidity of 100 TV and a calorimeter system that is 70 radiation lengths deep, equivalent to four nuclear interaction lengths, which extends the energy reach for cosmic-ray nuclei up to the PeV scale, i.e. beyond the cosmic-ray knee. Covering most of the sky continuously, AMS-100 will detect high-energy gamma rays in the calorimeter system and by pair conversion in the thin solenoid, reconstructed with excellent angular resolution in the silicon tracker.

Controlled clinical comparison of BacT/alert FA plus and FN plus blood culture media with BacT/alert FA and FN blood culture media.

New blood culture media containing antibiotic-binding polymeric beads have been developed for the BacT/Alert (bioMérieux, Inc., Durham, NC) blood culture system. To assess the performance of these new media, we compared the new BacT/Alert aerobic medium (FA Plus) with resins to BacT/Alert FA medium with activated charcoal and the new BacT/Alert anaerobic medium (FN Plus) to BacT/Alert FN medium at 3 tertiary care medical centers. Study bottle pairs were inoculated with a target volume of 6 to 10 ml of blood from adults and incubated in the BacT/Alert 3D blood culture instrument. In the FA Plus versus FA comparison, there were 1,507 study pairs. Among 170 isolates causing true bloodstream infections (BSIs), significantly more Staphylococcus aureus (P<0.001) and total microorganisms (P<0.01) grew in the FA Plus bottle than in the FA bottle. Fewer coagulase-negative staphylococcal (CoNS) contaminants grew in the FA Plus bottle than in the FA bottle (10 versus 22; P=0.05). In addition, growth was detected earlier in the FA Plus bottle than in the FA bottle (P<0.001). In the FN Plus versus FN comparison, there were 2,386 study pairs. Among 201 isolates causing true BSIs, significantly more S. aureus (P<0.001), CoNS (P<0.005), and total microorganisms (P<0.001) grew in the FN Plus bottle than in the FN bottle. Also, significantly more CoNS contaminants grew in the FN Plus bottle than in the FN bottle (P<0.001). Overall, microorganisms were detected earlier in the FN Plus than in the FN bottle (P<0.001). Medical technologists at all 3 study sites preferred the new media for Gram stain interpretation. We conclude that the FA Plus and FN Plus media provide improved and earlier detection of microorganisms compared with the FA and FN media and are preferable for Gram stain interpretation as well.

Update on blood cultures: how to obtain, process, report, and interpret.

The detection and identification of microorganisms circulating in the bloodstream of patients is arguably one of the most important functions of the clinical microbiology laboratory. Effective implementation of this function requires careful consideration of specimen collection and processing, culture techniques, result reporting, and, perhaps most importantly, result interpretation by the physician. The purpose of this review is to provide a synopsis of the current state of the art for each of these areas, with the intention of providing adequate information to enable clinical laboratory personnel and physicians to critically evaluate and, if required, improve their current blood culture practices.

Controlled multicenter evaluation of a bacteriophage-based method for rapid detection of Staphylococcus aureus in positive blood cultures.

Staphylococci are a frequent cause of bloodstream infections (BSIs). Appropriate antibiotic treatment for BSIs may be delayed because conventional laboratory testing methods take 48 to 72 h to identify and characterize isolates from positive blood cultures. We evaluated a novel assay based on bacteriophage amplification that identifies Staphylococcus aureus and differentiates between methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively) in samples taken directly from signal-positive Bactec blood culture bottles within 24 h of positive signal, with results available within 5 h. The performance of the MicroPhage KeyPath MRSA/MSSA blood culture test was compared to conventional identification and susceptibility testing methods. At four sites, we collectively tested a total of 1,165 specimens, of which 1,116 were included in our analysis. Compared to standard methods, the KeyPath MRSA/MSSA blood culture test demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 91.8%, 98.3%, 96.3%, and 96.1%, respectively, for correctly identifying S. aureus. Of those correctly identified as S. aureus (n = 334), 99.1% were correctly categorized as either MSSA or MRSA. Analysis of a subset of the data revealed that the KeyPath MRSA/MSSA blood culture test delivered results a median of 30 h sooner than conventional methods (a median of 46.9 h versus a median of 16.9 h). Although the sensitivity of the test in detecting S. aureus-positive samples is not high, its accuracy in determining methicillin resistance and susceptibility among positives is very high. These characteristics may enable earlier implementation of appropriate antibiotic treatment for many S. aureus BSI patients.

Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis.

Despite widespread use of antibiotics, few studies have measured their effects on the burden or diversity of bacteria in the mammalian intestine. We developed an oral antibiotic treatment protocol and characterized its effects on murine intestinal bacterial communities and immune cell homeostasis. Antibiotic administration resulted in a 10-fold reduction in the amount of intestinal bacteria present and sequencing of 16S rDNA segments revealed significant temporal and spatial effects on luminal and mucosal-associated communities including reductions in luminal Firmicutes and mucosal-associated Lactobacillus species, and persistence of bacteria belonging to the Bacteroidetes and Proteobacteria phyla. Concurrently, antibiotic administration resulted in reduced RELM beta production, and reduced production of interferon-gamma and interleukin-17A by mucosal CD4(+) T lymphocytes. This comprehensive temporal and spatial metagenomic analyses will provide a resource and framework to test the influence of bacterial communities in murine models of human disease.

Delineation of pilin domains required for bacterial association into microcolonies and intestinal colonization by Vibrio cholerae.

The toxin-co-regulated pilus (TCP), a type 4 pilus that is expressed by epidemic strains of Vibrio cholerae O1 and O139, is required for colonization of the human intestine. The TCP structure is assembled as a polymer of repeating subunits of TcpA pilin that form long fibres, which laterally associate into bundles. Previous passive immunization studies have suggested that the C-terminal region of TcpA is exposed on the surface of the pilus fibre and has a critical role in mediating the colonization functions of TCP. In the present study, we have used site-directed mutagenesis to delineate two domains within the C-terminal region that contribute to TCP structure and function. Alterations in the first domain, termed the structural domain, result in altered pilus stability or morphology. Alterations in the second domain, termed the interaction domain, affect colonization and/or infection by CTX-bacteriophage without affecting pilus morphology. In vitro and in vivo analyses of the tcpA mutants revealed that a major function of TCP is to mediate bacterial interaction through direct pilus-pilus contact required for microcolony formation and productive intestinal colonization. The importance of this function is supported by the finding that intragenic suppressor mutations that restore colonization ability to colonization-deficient mutants simultaneously restore pilus-mediated bacterial interactions. The alterations resulting from the suppressor mutations also provide insight into the molecular interactions between pilin subunits within and between pilus fibres.