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Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

FMOF-1 is a flexible, superhydrophobic metal-organic framework with a network of channels and side pockets decorated with -CF 3 groups. CO 2 adsorption isotherms measured between 278 and 313 K and up to 55 bar reveal a maximum uptake of ca. 6.16 mol kg -1 (11.0 mol L -1 ) and unusual isotherm shapes at the higher temperatures, suggesting framework expansion. We used neutron diffraction and molecular simulations to investigate the framework expansion behaviour and the accessibility of the small pockets to N 2 , O 2 , and CO 2 . Neutron diffraction in situ experiments on the crystalline powder show that CO 2 molecules are favourably adsorbed at three distinct adsorption sites in the large channels of FMOF-1 and cannot access the small pockets in FMOF-1 at 290 K and oversaturated pressure at 61 bar. Stepped adsorption isotherms for N 2 and O 2 at 77 K can be explained by combining Monte Carlo simulations in several different crystal structures of FMOF-1 obtained from neutron and X-ray diffraction under different conditions. A similar analysis is successful for CO 2 adsorption at 278 and 283 K up to ca. 30 bar; however, at 298 K and pressures above 30 bar, the results suggest even more substantial expansion of the FMOF-1 framework. The measured contact angle for water on an FMOF-1 pellet is 158°, demonstrating superhydrophobicity. Simulations and adsorption measurements also show that FMOF-1 is hydrophobic and water is not adsorbed in FMOF-1 at room temperature. Simulated mixture isotherms of CO 2 in the presence of 80% relative humidity predict that water does not influence the CO 2 adsorption in FMOF-1, suggesting that hydrophobic MOFs could hold promise for CO 2 capture from humid gas streams.

We present results from a comprehensive submillimeter spectral survey toward the source Orion South, based on data obtained with the HIFI instrument aboard the Herschel Space Observatory , covering the frequency range 480 to 1900 GHz. We detect 685 spectral lines with S/N > 3 σ , originating from 52 different molecular and atomic species. We model each of the detected species assuming conditions of Local Thermodynamic Equilibrium. This analysis provides an estimate of the physical conditions of Orion South (column density, temperature, source size, & V LSR ). We find evidence for three different cloud components: a cool (T ex ~ 20 - 40 K), spatially extended (> 60″), and quiescent (Δ V FWHM ~ 4 km s -1 ) component; a warmer (T ex ~ 80 - 100 K), less spatially extended (~ 30″), and dynamic (Δ V FWHM ~ 8 km s -1 ) component, which is likely affected by embedded outflows; and a kinematically distinct region (T ex > 100 K; V LSR ~ 8 km s -1 ), dominated by emission from species which trace ultraviolet irradiation, likely at the surface of the cloud. We find little evidence for the existence of a chemically distinct "hot core" component, likely due to the small filling factor of the hot core or hot cores within the Herschel beam. We find that the chemical composition of the gas in the cooler, quiescent component of Orion South more closely resembles that of the quiescent ridge in Orion-KL. The gas in the warmer, dynamic component, however, more closely resembles that of the Compact Ridge and Plateau regions of Orion-KL, suggesting that higher temperatures and shocks also have an influence on the overall chemistry of Orion South.

One of the key issues in studying transcriptional regulation during development is how to employ genome-wide assays that reveals sites of open chromatin and transcription factor binding to efficiently identify biologically relevant genes and enhancers. Analysis of Drosophila CNS midline cell development provides a useful system for studying transcriptional regulation at the genomic level due to a large, well-characterized set of midline-expressed genes and in vivo validated enhancers. In this study, FAIRE-seq on FACS-purified midline cells was performed and the midline FAIRE data were compared with whole-embryo FAIRE data. We find that regions of the genome with a strong midline FAIRE peak and weak whole-embryo FAIRE peak overlap with known midline enhancers and provide a useful predictive tool for enhancer identification. In a complementary analysis, we compared a large dataset of fragments that drive midline expression in vivo with the FAIRE data. Midline enhancer fragments with a midline FAIRE peak tend to be near midline-expressed genes, whereas midline enhancers without a midline FAIRE peak were often distant from midline-expressed genes and unlikely to drive midline transcription in vivo., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)

The vibrational spectrum of ammonia has received an enormous amount of attention due to its potential prevalence in hot exo-planet atmospheres and persistent challenges in assigning and modeling highly excited and often highly perturbed states. Effective Hamiltonian models face challenges due to strong coupling between the large amplitude inversion and the other small amplitude vibrations. To date, only the ground and ν 2 positions could be modeled to experimental accuracy using effective Hamiltonians. Several previous attempts to analyze the 2ν 2 and ν 4 energy levels failed to model both the microwave and infrared transitions to experimental accuracy. In this work, we performed extensive experimental measurements and data analysis for the 2ν 2 and ν 4 inversion-rotation and vibrational transitions. We measured 159 new transition frequencies with microwave precision and assigned 1680 new ones from existing Fourier transform spectra recorded in Synchrotron SOLEIL. The newly assigned data significantly expand the range of assigned quantum numbers; combined with all the previously published high-resolution data, the 2ν 2 and ν 4 states are reproduced to experimental accuracy using a global model described here. Achieving experimental accuracy required inclusion of a number of terms in the effective Hamiltonian that were neglected in previous work. These terms have also been neglected in the analysis of states higher than 2ν 2 and ν 4 suggesting that the inversion-rotation-vibration spectrum of ammonia may be far more tractable to effective Hamiltonians than previously believed.

From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2014 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 952 unique episodes of bacteraemia investigated, 94.4% were caused by either E. faecalis (54.9%) or E. faecium (39.9%). Ampicillin resistance was detected in 0.6% of E. faecalis and in 89.4% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 46.1% of E. faecalis and E. faecium respectively. Overall 51.1% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 81.5% harboured vanB genes and 18.5% vanA genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 113 pulsed-field gel electrophoresis pulsotypes of which 68.9% of isolates were classified into 14 major pulsotypes containing 5 or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. The geographical distribution of the 4 predominant sequence types (ST203, ST796, ST555 and ST17) varied with only ST203 identified across most regions of Australia. Overall 74.7% of isolates belonging to the four predominant STs harboured vanA or vanB genes. In conclusion, the AESOP 2014 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium, which have limited treatment options.

From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2014 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and to characterise the molecular epidemiology of the isolates. Overall, 18.8% of the 2,206 SAB episodes were methicillin resistant, which was significantly higher than that reported in most European countries. The 30-day all-cause mortality associated with methicillin-resistant SAB was 23.4%, which was significantly higher than the 14.4% mortality associated with methicillin-sensitive SAB (P <0.0001). With the exception of the beta-lactams and erythromycin, antimicrobial resistance in methicillin-sensitive S. aureus remains rare. However in addition to the beta-lactams, approximately 50‰ of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 15% were resistant to co-trimoxazole, tetracycline and gentamicin. When applying the European Committee on Antimicrobial Susceptibility Testing breakpoints, teicoplanin resistance was detected in 2 S. aureus isolates. Resistance was not detected for vancomycin or linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to 2 healthcare-associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has become the predominant healthcare associated clone in Australia. Sixty per cent of methicillin-resistant SAB were due to community-associated (CA) clones. Although polyclonal, almost 44% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. As CA-MRSA is well established in the Australian community it is important that antimicrobial resistance patterns in community and healthcare-associated SAB is monitored as this information will guide therapeutic practices in treating S. aureus sepsis.

From 1 January to 31 December 2013, around Australia 26 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2013 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, (with particular emphasis on susceptibility to methicillin) and to characterise the molecular epidemiology of the isolates. Overall 19.1% of the 2,010 SAB episodes were methicillin resistant, which is significantly higher than that reported in most European countries. Although the SAB 30-day all cause mortality appears to be decreasing in Australia, methicillin-resistant SAB associated mortality remains high (20.1%) and was significantly higher than methicillin-sensitive SAB associated mortality (13%) (P< 0.0001). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin sensitive S. aureus remains rare. However, in addition to the ß-lactams, approximately 50% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 20% were resistant to co-trimoxazole, tetracycline and gentamicin. Linezolid, daptomycin and teicoplanin resistance was detected in a small number of S. aureus isolates. Resistance to vancomycin was not detected. Resistance was largely attributable to 2 healthcare associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has now become the predominant healthcare associated clone in Australia. Approximately 60% of methicillin-resistant SAB were due to community associated clones. Although polyclonal, almost 50% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. As CA-MRSA is well established in the Australian community, it is important antimicrobial resistance patterns in community and healthcare associated SAB is monitored as this information will guide therapeutic practices in treating S. aureus sepsis., (This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.)

From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options., (This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.)

Background: Staphylococcus aureus infection is known to play a role in recalcitrant chronic rhinosinusitis (CRS). However, it is unknown if recurrent S. aureus infections are caused by the same strain or are due to independent acquisitions of different strains., Methods: Samples were collected from patients with CRS from July 2011 to August 2012. S. aureus was isolated from mucosal swabs and tissue specimens from patients who underwent surgery during the study period, or from swabs of areas of purulence taken in the postoperative period under endoscopic guidance. Pulsed-field gel electrophoresis was used to characterize S. aureus isolates., Results: Thirty-four patients were included in the study; 79% showed persistence of the same S. aureus strain in their paranasal sinuses (p = 0.001; H1 ≠ 50%). Furthermore, a significantly high frequency of patients with known biofilm status were positive for S. aureus biofilm (p = 0.002; H1 ≠ 50%). When patients were stratified according to disease evolution postsurgery, certain strains appeared to be more commonly associated with symptom persistence., Conclusion: The same S. aureus strain appears to persist in the paranasal sinuses of CRS patients despite multiple courses of culture-directed antibiotics. This suggests that conventional antimicrobial therapies in patients with CRS may not eliminate the organism. This may be partly explained by the formation of biofilms in the paranasal sinus region., (© 2014 ARS-AAOA, LLC.)

From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

Transcriptional enhancers integrate information derived from transcription factor binding to control gene expression. One key question concerns the extent of trans- and cis-regulatory variation in how co-expressed genes are controlled. The Drosophila CNS midline cells constitute a group of neurons and glia in which expression changes can be readily characterized during specification and differentiation. Using a transgenic approach, we compare the cis-regulation of multiple genes expressed in the Drosophila CNS midline primordium cells, and show that while the expression patterns may appear alike, the target genes are not equivalent in how these common expression patterns are achieved. Some genes utilize a single enhancer that promotes expression in all midline cells, while others utilize multiple enhancers with distinct spatial, temporal, and quantitative contributions. Two regulators, Single-minded and Notch, play key roles in controlling early midline gene expression. While Single-minded is expected to control expression of most, if not all, midline primordium-expressed genes, the role of Notch in directly controlling midline transcription is unknown. Midline primordium expression of the rhomboid gene is dependent on cell signaling by the Notch signaling pathway. Mutational analysis of a rhomboid enhancer reveals at least 5 distinct types of functional cis-control elements, including a binding site for the Notch effector, Suppressor of Hairless. The results suggest a model in which Notch/Suppressor of Hairless levels are insufficient to activate rhomboid expression by itself, but does so in conjunction with additional factors, some of which, including Single-minded, provide midline specificity to Notch activation. Similarly, a midline glial enhancer from the argos gene, which is dependent on EGF/Spitz signaling, is directly regulated by contributions from both Pointed, the EGF transcriptional effector, and Single-minded. In contrast, midline primordium expression of other genes shows a strong dependence on Single-minded and varying combinations of additional transcription factors. Thus, Single-minded directly regulates midline primordium-expressed genes, but in some cases plays a primary role in directing target gene midline expression, and in others provides midline specificity to cell signaling inputs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To compare the management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in patients known to be MRSA-colonized/infected (C-patients) with the management and outcome in those not known to be colonized/infected (NC-patients), we conducted a 10-year retrospective review of MRSA bacteraemia in an adult tertiary hospital. Clinical data were obtained by chart review, and mortality data from linked databases. Prior MRSA colonization/infection status was available to treating clinicians at the time of the bacteraemia as a 'Micro-Alert' tag on the patient's labels, in medical charts, and in electronic information systems. C-patients accounted for 35.4% of all MRSA bacteraemia episodes. C-patients were more likely to be indigenous, to be diabetic, or to have a history of previous S. aureus infection. Markers of illness severity (Simplified Acute Physiology Score (SAPS)-II, need for admission to the intensive-care unit, length of stay, and metastatic seeding) were similar in both groups. Empirical therapy included a glycopeptide in 49.3% of C-patients vs. 18.9% of NC-patients (p <0.01), and contained an antibiotic to which the MRSA isolate tested susceptible in vitro in 56.7% of C-patients vs. 45.1% of NC-patients (p 0.13). All-cause 7-day and 30-day mortality were 7.5% vs. 18.9% (p 0.04), and 22.4% vs. 31.1% (p 0.20), in the C-patient and NC-patient groups, respectively. Knowing MRSA colonization status was significantly associated with lower 30-day mortality in Cox regression analysis (p <0.01). These data suggest that mortality from MRSA bacteraemia is lower in C-patients, which may reflect the earlier use of glycopeptides. The low use of empirical glycopeptides in septic patients known to be previously MRSA-colonized/infected may represent a missed opportunity for infection control to positively impact on clinical management., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

A major limitation in understanding embryonic development is the lack of cell type-specific markers. Existing gene expression and marker atlases provide valuable tools, but they typically have one or more limitations: a lack of single-cell resolution; an inability to register multiple expression patterns to determine their precise relationship; an inability to be upgraded by users; an inability to compare novel patterns with the database patterns; and a lack of three-dimensional images. Here, we develop new 'atlas-builder' software that overcomes each of these limitations. A newly generated atlas is three-dimensional, allows the precise registration of an infinite number of cell type-specific markers, is searchable and is open-ended. Our software can be used to create an atlas of any tissue in any organism that contains stereotyped cell positions. We used the software to generate an 'eNeuro' atlas of the Drosophila embryonic CNS containing eight transcription factors that mark the major CNS cell types (motor neurons, glia, neurosecretory cells and interneurons). We found neuronal, but not glial, nuclei occupied stereotyped locations. We added 75 new Gal4 markers to the atlas to identify over 50% of all interneurons in the ventral CNS, and these lines allowed functional access to those interneurons for the first time. We expect the atlas-builder software to benefit a large proportion of the developmental biology community, and the eNeuro atlas to serve as a publicly accessible hub for integrating neuronal attributes - cell lineage, gene expression patterns, axon/dendrite projections, neurotransmitters--and linking them to individual neurons., (© 2014. Published by The Company of Biologists Ltd.)

In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL negative CA-MRSA infection (55.7 years, 95% CI 50.7-60.6). This shift in the molecular epidemiology of MRSA clones in the Australian community will potentially increase the number of young Australians with skin and soft tissue infections requiring hospitalisation., (copyright@health.gov.au)

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2011 survey focussed on hospital-onset infections, examining isolates from all specimens presumed to be causing disease. In 2011, 1,827 Escherichia coli, 537 Klebsiella species and 269 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibilty to the third-generation cephalosporin, ceftriaxone, was found in 9.6% of E. coli and 9.5%-12.1% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 10.6% for E. coli, 0.0%-8.3% for Klebsiella spp. and 0.0%-5.0% in Enterobacter spp. Resistance rates to gentamicin were 8.6%, 2.9%-10.9%, and 0.0%-15.6% for the same 3 groups respectively. Eight strains, 5 Klebsiella spp. and 3 Enterobacter spp. were shown to harbour a carbapenemase (IMP-4)., (copyright@health.gov.au)

Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2010 survey focussed on community-onset infections, examining isolates from urinary tract infections from patients presenting to outpatient clinics, emergency departments or to community practitioners. Two thousand and ninety-two Escherichia coli, 578 Klebsiella species and 268 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 3.2% of E. coli and 3.2%-4.0% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 5.4% for E. coli, 1.0%-2.3% for Klebsiella spp., and 2.5%-6.6% in Enterobacter spp, and resistance rates to piperacillin-tazobactam were 2.8%, 3.2%-6.9%, and 16.8%-18.0% for the same 3 groups respectively. Only 3 strains, 2 Klebsiella spp. and 1 Enterobacter spp, were shown to harbour a carbapenemase (IMP-4)., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

In 2010, 15 institutions around Australia conducted a period prevalence study of key resistances in isolates of Enterococcus species associated with a range of clinical disease amongst in- and outpatients. Each institution collected up to 100 consecutive isolates and tested these for susceptibility to commonly used antimicrobials using standardised methods. Vancomycin-resistant Enterococcus faecium and Enterococcus faecalis were characterised by pulsed-field gel electrophoresis. Multilocus sequence typing was performed on representative pulsotypes of E. faecium. Susceptibility results were compared with similar surveys conducted in 1995, 1999, 2003, 2005, 2007 and 2009. In the 2010 survey, E. faecalis (1,201 isolates) and E. faecium (170 isolates) made up 98.9% of the 1,386 isolates tested. Ampicillin resistance was very common (85.3%) in E. faecium and absent in E. faecalis. Non-susceptibility to vancomycin was 36.5% in E. faecium (similar to the 35.2% in 2009 but up from 15.4% in the 2007 survey) and 0.5% in E. faecalis. There were significant differences in the proportion of vancomycin-resistant E. faecium between the states ranging from 0% in Western Australia to 54.4% in South Australia. The vanB gene was detected in 62 E. faecium and 3 E. faecalis isolates. The vanA gene was detected in 1 E. faecium isolate. All vancomycin-resistant E. faecium belonged to clonal complex 17. The most common sequence type (ST) was ST203, which was found in all regions that had reports of vancomycin resistant enterococci. ST341 was detected only in New South Wales/Australian Capital Territory and ST414 only in South Australia and Victoria. High-level resistance to gentamicin was 34.1% in E. faecalis and 66.1% in E. faecium. A subset of isolates was tested against high-level streptomycin, linezolid and quinupristin/dalfopristin. High-level streptomycin resistance was found in 8.2% of E. faecalis isolates and 43.8% of E. faecium isolates. Linezolid non-susceptibility was more common in E. faecalis (5.8%) than E. faecium (0.9%). Overall 9.4% of E. faecium were resistant to quinupristin/dalfopristin (E. faecalis is intrinsically resistant)., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

In 2011, the Australian Group on Antimicrobial Resistance (AGAR) conducted a period-prevalence survey of clinical Staphylococcus aureus isolated from hospital inpatients. Twenty-nine microbiology laboratories from all states and mainland territories participated. Specimens were collected more than 48 hours post-admission. Isolates were tested by Vitek2® antimicrobial susceptibility card (AST-P612 card). Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) was 30.3%; ranging from 19.9% in Western Australia to 36.8% in New South Wales/Australian Capital Territory. Resistance to the non-ß-lactam antimicrobials was common except for rifampicin, fusidic acid, high-level mupirocin and daptomycin. No resistance was detected for vancomycin, teicoplanin or linezolid. Antibiotic resistance in methicillin susceptible S. aureus (MSSA) was rare apart from erythromycin (13.2%) and there was no resistance to vancomycin, teicoplanin or linezolid. Inducible clindamycin resistance was the norm for erythromycin resistant, clindamycin intermediate/susceptible S. aureus in Australia with 90.6% of MRSA and 83.1% of MSSA with this phenotype having a positive double disc diffusion test (D-test). The proportion of S. aureus characterised as being healthcare-associated MRSA (HA-MRSA) was 18.2%, ranging from 4.5% in Western Australia to 28.0% in New South Wales/Australian Capital Territory. Four HA-MRSA clones were characterised and 98.8% of HA-MRSA isolates were classified as either ST22-IV [2B] (EMRSA-15) or ST239-III [3A] (Aus-2/3 EMRSA). Multiclonal community-associated MRSA (CA-MRSA) accounted for 11.7% of all S. aureus. In Australia, regional variation in resistance is due to the differential distribution of MRSA clones between regions, particularly for the major HA-MRSA clone, ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

The Australian Group on Antimicrobial Resistance (AGAR) performs regular multicentre period prevalence studies to monitor changes in antimicrobial resistance. In 2011, 29 laboratories in Australia participated in the national surveillance of Staphylococcus aureus resistance. The survey only included unique isolates from clinical specimens collected ≥48h after hospital admission. MRSA accounted for 30.3% of S. aureus isolates. MRSA resistance to ciprofloxacin, erythromycin, tetracycline, trimethoprim/sulfamethoxazole, gentamicin and clindamycin (constitutive resistance) varied considerably between regions. Resistance to non-β-lactam antimicrobials was uncommon in MSSA, with the exception of erythromycin. Regional variation in resistance was due to the differential distribution of MRSA clones between regions. The proportion of S. aureus genetically characterised as healthcare-associated MRSA (HA-MRSA) was significantly lower in this survey (18.2%) compared with the 2005 survey (24.2%) (P<0.0001). Although four HA-MRSA clones were characterised, 98.8% of HA-MRSA were classified as either ST22-MRSA-IV [2B] (EMRSA-15) or ST239-MRSA-III [3A] (Aus-2/3 EMRSA). Multiclonal community-associated MRSA (CA-MRSA) increased markedly from 6.5% in 2005 to 11.7% of all S. aureus in 2011 (P<0.0001). Although the proportion of MRSA resistant to non-β-lactam antimicrobials has decreased nationally, the proportion of S. aureus that are MRSA has remained stable. This is primarily due to non-multiresistant CA-MRSA becoming more common in Australian hospitals at the expense of the long-established multiresistant ST239-MRSA-III [3A] (Aus-2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be extremely rare, it is most likely that patients colonised at admission with CA-MRSA have become infected with the colonising strain during their hospital stay., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Many algorithms analyze enhancers for overrepresentation of known and novel motifs, with the goal of identifying binding sites for direct regulators of gene expression. Twine is a Java GUI with multiple graphical representations ('Views') of enhancer alignments that displays motifs, as IUPAC consensus sequences or position frequency matrices, in the context of phylogenetic conservation to facilitate cis-regulatory element discovery. Thresholds of phylogenetic conservation and motif stringency can be altered dynamically to facilitate detailed analysis of enhancer architecture. Views can be exported to vector graphics programs to generate high-quality figures for publication. Twine can be extended via Java plugins to manipulate alignments and analyze sequences., Availability: Twine is freely available as a compiled Java .jar package or Java source code at http://labs.bio.unc.edu/crews/twine/., Supplementary Information: Supplementary data are available at Bioinformatics online.

Here, we describe the embryonic central nervous system expression of 5,000 GAL4 lines made using molecularly defined cis-regulatory DNA inserted into a single attP genomic location. We document and annotate the patterns in early embryos when neurogenesis is at its peak, and in older embryos where there is maximal neuronal diversity and the first neural circuits are established. We note expression in other tissues, such as the lateral body wall (muscle, sensory neurons, and trachea) and viscera. Companion papers report on the adult brain and larval imaginal discs, and the integrated data sets are available online (http://www.janelia.org/gal4-gen1). This collection of embryonically expressed GAL4 lines will be valuable for determining neuronal morphology and function. The 1,862 lines expressed in small subsets of neurons (<20/segment) will be especially valuable for characterizing interneuronal diversity and function, because although interneurons comprise the majority of all central nervous system neurons, their gene expression profile and function remain virtually unexplored., (Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.)

To determine the impact of infectious diseases consultation (IDC) in Staphylococcus aureus bacteraemia. All MRSA bacteraemia and a random subset of MSSA bacteraemia were retrospectively analysed. Out of 599 SAB episodes, 162 (27%) were followed by an IDC. Patients with IDC were younger and more frequently intravenous drug users, but fewer resided in a long-term care facility or were indigenous. Hospital length of stay was longer (29.5 vs 17 days, p < 0.001), and endocarditis (19.1% vs 7.3%, p < 0.001) and metastatic seeding (22.2% vs 10.1%, p < 0.001) were more frequent in the IDC group; however, SAPS II scores were lower in the IDC group (27 vs 37, p < 0.001). ICU admission rates in the two groups were similar. The isolate tested susceptible to empirical therapy more frequently in the IDC group (88.9% vs 78.0%, p = 0.003). Seven-day (3.1 vs 16.5%), 30-day (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC group (all p < 0.001). Multivariate analysis showed that effective initial therapy was the only variable associated with the protective effect of IDC. In patients with SAB, all-cause mortality was significantly lower in patients who had an IDC, because of the higher proportion of patients receiving effective initial antibiotics.

The Drosophila Zelda transcription factor plays an important role in regulating transcription at the embryonic maternal-to-zygotic transition. However, expression of zelda continues throughout embryogenesis in cells including the developing CNS and trachea, but little is known about its post-blastoderm functions. In this paper, it is shown that zelda directly controls CNS midline and tracheal expression of the link (CG13333) gene, as well as link blastoderm expression. The link gene contains a 5' enhancer with multiple Zelda TAGteam binding sites that in vivo mutational studies show are required for link transcription. The link enhancer also has a binding site for the Single-minded:Tango and Trachealess:Tango bHLH-PAS proteins that also influences link midline and tracheal expression. These results provide an example of how a transcription factor (Single-minded or Trachealess) can interact with distinct co-regulatory proteins (Zelda or Sox/POU-homeodomain proteins) to control a similar pattern of expression of different target genes in a mechanistically different manner. While zelda and single-minded midline expression is well-conserved in Drosophila, midline expression of link is not well-conserved. Phylogenetic analysis of link expression suggests that ~60 million years ago, midline expression was nearly or completely absent, and first appeared in the melanogaster group (including D. melanogaster, D. yakuba, and D. erecta) >13 million years ago. The differences in expression are due, in part, to sequence polymorphisms in the link enhancer and likely due to altered binding of multiple transcription factors. Less than 6 million years ago, a second change occurred that resulted in high levels of expression in D. melanogaster. This change may be due to alterations in a putative Zelda binding site. Within the CNS, the zelda gene is alternatively spliced beginning at mid-embryogenesis into transcripts that encode a Zelda isoform missing three zinc fingers from the DNA binding domain. This may result in a protein with altered, possibly non-functional, DNA-binding properties. In summary, Zelda collaborates with bHLH-PAS proteins to directly regulate midline and tracheal expression of an evolutionary dynamic enhancer in the post-blastoderm embryo., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: It is uncertain whether particular clones causing invasive community-onset methicillin-resistant and methicillin-sensitive Staphylococcus aureus (cMRSA/cMSSA) infection differ in virulence., Methods: Invasive cMRSA and cMSSA cases were prospectively identified. Principal component analysis was used to derive an illness severity score (ISS) from clinical data, including 30-day mortality, requirement for intensive hospital support, the presence of bloodstream infection, and hospital length of stay. The mean ISS for each S. aureus clone (based on MLST) was compared with its DNA microarray-based genotype., Results: Fifty-seven cMRSA and 50 cMSSA infections were analyzed. Ten clones caused 82 (77%) of these infections and had an ISS calculated. The enterotoxin gene cluster (egc) and the collagen adhesin (cna) gene were found in 4 of the 5 highest-ranked clones (ST47-MSSA, ST30-MRSA-IV[2B], ST45-MSSA, and ST22-MRSA-IV[2B]) compared with none and 1 of the lowest 5 ranked clones, respectively. cMSSA clones caused more severe infection than cMRSA clones. The lukF/lukS Panton-Valentine leukocidin (PVL) genes did not directly correlate with the ISS, being present in the second, fourth, and 10th most virulent clones., Conclusions: The clinical severity of invasive cMRSA and cMSSA infection is likely to be attributable to the isolates' entire genotype rather than a single putative virulence determinant such as PVL.

The Drosophila CNS midline glia (MG) are multifunctional cells that ensheath and provide trophic support to commissural axons, and direct embryonic development by employing a variety of signaling molecules. These glia consist of two functionally distinct populations: the anterior MG (AMG) and posterior MG (PMG). Only the AMG ensheath axon commissures, whereas the function of the non-ensheathing PMG is unknown. The Drosophila MG have proven to be an excellent system for studying glial proliferation, cell fate, apoptosis, and axon-glial interactions. However, insight into how AMG migrate and acquire their specific positions within the axon-glial scaffold has been lacking. In this paper, we use time-lapse imaging, single-cell analysis, and embryo staining to comprehensively describe the proliferation, migration, and apoptosis of the Drosophila MG. We identified 3 groups of MG that differed in the trajectories of their initial inward migration: AMG that migrate inward and to the anterior before undergoing apoptosis, AMG that migrate inward and to the posterior to ensheath commissural axons, and PMG that migrate inward and to the anterior to contact the commissural axons before undergoing apoptosis. In a second phase of their migration, the surviving AMG stereotypically migrated posteriorly to specific positions surrounding the commissures, and their final position was correlated with their location prior to migration. Most noteworthy are AMG that migrated between the commissures from a ventral to a dorsal position. Single-cell analysis indicated that individual AMG possessed wide-ranging and elaborate membrane extensions that partially ensheathed both commissures. These results provide a strong foundation for future genetic experiments to identify mutants affecting MG development, particularly in guidance cues that may direct migration. Drosophila MG are homologous in structure and function to the glial-like cells that populate the vertebrate CNS floorplate, and study of Drosophila MG will provide useful insights into floorplate development and function., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Developmental regulatory proteins are commonly utilized in multiple cell types throughout development. The Drosophila single-minded (sim) gene acts as master regulator of embryonic CNS midline cell development and transcription. However, it is also expressed in the brain during larval development. In this paper, we demonstrate that sim is expressed in three clusters of anterior central brain neurons: DAMv1/2, BAmas1/2, and TRdm and in three clusters of posterior central brain neurons: a subset of DPM neurons, and two previously unidentified clusters, which we term PLSC and PSC. In addition, sim is expressed in the lamina and medulla of the optic lobes. MARCM studies confirm that sim is expressed at high levels in neurons but is low or absent in neuroblasts (NBs) and ganglion mother cell (GMC) precursors. In the anterior brain, sim(+) neurons are detected in 1st and 2nd instar larvae but rapidly increase in number during the 3rd instar stage. To understand the regulation of sim brain transcription, 12 fragments encompassing 5'-flanking, intronic, and 3'-flanking regions were tested for the presence of enhancers that drive brain expression of a reporter gene. Three of these fragments drove expression in sim(+) brain cells, including all sim(+) neuronal clusters in the central brain and optic lobes. One fragment upstream of sim is autoregulatory and is expressed in all sim(+) brain cells. One intronic fragment drives expression in only the PSC and laminar neurons. Another downstream intronic fragment drives expression in all sim(+) brain neurons, except the PSC and lamina. Thus, together these two enhancers drive expression in all sim(+) brain neurons. Sequence analysis of existing sim mutant alleles identified three likely null alleles to utilize in MARCM experiments to examine sim brain function. Mutant clones of DAMv1/2 neurons revealed a consistent axonal fasciculation defect. Thus, unlike the embryonic roles of sim that control CNS midline neuron and glial formation and differentiation, postembryonic sim, instead, controls aspects of axon guidance in the brain. This resembles the roles of vertebrate sim that have an early role in neuronal migration and a later role in axonogenesis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Icy bodies may have delivered the oceans to the early Earth, yet little is known about water in the ice-dominated regions of extrasolar planet-forming disks. The Heterodyne Instrument for the Far-Infrared on board the Herschel Space Observatory has detected emission lines from both spin isomers of cold water vapor from the disk around the young star TW Hydrae. This water vapor likely originates from ice-coated solids near the disk surface, hinting at a water ice reservoir equivalent to several thousand Earth oceans in mass. The water's ortho-to-para ratio falls well below that of solar system comets, suggesting that comets contain heterogeneous ice mixtures collected across the entire solar nebula during the early stages of planetary birth.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was first reported in remote regions of Western Australia and is now the predominant MRSA isolated in the state. The objective of this study is to determine the genetic relatedness of Western Australian CA-MRSA clones within different multilocus sequence type (MLST) clonal clusters providing an insight into the frequency of S. aureus SCCmec acquisition within a region., Results: The CA-MRSA population in Western Australia is genetically diverse consisting of 83 unique pulsed-field gel electrophoresis strains from which 46 MLSTs have been characterised. Forty five of these sequence types are from 18 MLST clonal clusters and two singletons. While SCCmec IV and V are the predominant SCCmec elements, SCCmec VIII and several novel and composite SCCmec elements are present. The emergence of MRSA in diverse S. aureus clonal clusters suggests horizontal transmission of the SCCmec element has occurred on multiple occasions. Furthermore DNA microarray and spa typing suggests horizontal transfer of SCCmec elements has also occurred within the same CC. For many single and double locus variant CA-MRSA clones only a few isolates have been detected., Conclusions: Although multiple CA-MRSA clones have evolved in the Western Australian community only three clones have successfully adapted to the Western Australian community environment. These data suggest the successful evolution of a CA-MRSA clone may not only depend on the mobility of the SCCmec element but also on other genetic determinants.

In 2009, the Australian Group on Antimicrobial Resistance (AGAR) conducted a period-prevalence survey of clinical Staphylococcus aureus isolated from hospital inpatients. Thirty medical microbiology laboratories from each state and mainland territory participated. Specimens were collected more than 48 hours post-admission. Isolates were tested by Vitek2 (AST-P579 card) and by Etest for daptomycin. Nationally, the proportion of S. aureus that were MRSA was 33.6%, ranging from 27.3% in South Australia to 41.4% in New South Wales/Australian Capital Territory. Resistance to the non-beta-lactam antimicrobials was common except for rifampicin, fusidic acid, daptomycin and high-level mupirocin. No resistance was detected for vancomycin, teicoplanin, quinupristin-dalfopristin or linezolid. Resistance in the methicillin susceptible S. aureus (MSSA) was rare apart from erythromycin (12%) and absent for vancomycin, teicoplanin, daptomycin, quinupristin-dalfopristin and linezolid. The proportion of methicillin resistant S. aureus (MRSA) has remained stable since the first AGAR inpatient survey in 2005 yet during the same time frame resistance to many antimicrobials, in particular tetracycline, trimethoprim-sulphamethoxazole and gentamicin, has significantly decreased. This suggests that non-multi-resistant community-associated MRSA (CA-MRSA) clones are becoming more common in the hospital setting and replacing the long-established multi-resistant clones such as ST239-III (Aus 2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be extremely rare it is most likely that patients colonised at admission with CA-MRSA have become infected with the colonising strain during their hospital stay.

We report the first demonstration of a continuous wave coherent source covering 2.48-2.75 THz, with greater than 10% instantaneous tuning bandwidth and having 1-14 μW of output power at room temperature. This source is based on a 91.8-101.8 GHz synthesizer followed by a power amplifier and three cascaded frequency triplers. It demonstrates for the first time that purely electronic solid-state sources can generate a useful amount of power in a region of the electromagnetic spectrum where lasers (solid state or gas) were previously the only available coherent sources. The bandwidth, agility, and operability of this THz source have enabled wideband, high resolution spectroscopic measurements of water, methanol, and carbon monoxide with a resolution and signal-to-noise ratio unmatched by any other existing system, providing new insight in the physics of these molecules. Furthermore, the power and optical beam quality are high enough to observe the Lamb-dip effect in water. The source frequency has an absolute accuracy better than 1 part in 10(12) and the spectrometer achieves sub-Doppler frequency resolution better than 1 part in 10(8). The harmonic purity is better than 25 dB. This source can serve as a coherent signal for absorption spectroscopy, a local oscillator for a variety of heterodyne systems and can be used as a method for precision control of more powerful but much less frequency agile quantum mechanical terahertz sources., (© 2011 American Institute of Physics)

Complete and reliable knowledge of the ammonia spectrum is needed to enable the analysis and interpretation of astrophysical and planetary observations. Ammonia has been observed in the interstellar medium up to J=18 and more highly excited transitions are expected to appear in hot exoplanets and brown dwarfs. As a result, there is considerable interest in observing and assigning the high J (rovibrational) spectrum. In this work, numerous spectroscopic techniques were employed to study its high J transitions in the ground and ν(2)=1 states. Measurements were carried out using a frequency multiplied submillimeter spectrometer at Jet Propulsion Laboratory (JPL), a tunable far-infrared spectrometer at University of Toyama, and a high-resolution Bruker IFS 125 Fourier transform spectrometer (FTS) at Synchrotron SOLEIL. Highly excited ammonia was created with a radiofrequency discharge and a dc discharge, which allowed assignments of transitions with J up to 35. One hundred and seventy seven ground state and ν(2)=1 inversion transitions were observed with microwave accuracy in the 0.3-4.7 THz region. Of these, 125 were observed for the first time, including 26 ΔK=3 transitions. Over 2000 far-infrared transitions were assigned to the ground state and ν(2)=1 inversion bands as well as the ν(2) fundamental band. Of these, 1912 were assigned using the FTS data for the first time, including 222 ΔK=3 transitions. The accuracy of these measurements has been estimated to be 0.0003-0.0006 cm(-1). A reduced root mean square error of 0.9 was obtained for a global fit of the ground and ν(2)=1 states, which includes the lines assigned in this work and all previously available microwave, terahertz, far-infrared, and mid-infrared data. The new measurements and predictions reported here will support the analyses of astronomical observations by high-resolution spectroscopy telescopes such as Herschel, SOFIA, and ALMA. The comprehensive experimental rovibrational energy levels reported here will permit further refinement of the potential energy surface to improve ammonia ab initio calculations and facilitate assignment of new high-resolution spectra of hot ammonia.

The rotational spectrum of n-propanol (n-CH(3)CH(2)CH(2)OH) was studied with several techniques of contemporary broadband rotational spectroscopy at frequencies from 8 to 550 GHz. Rotational transitions in all five conformers of the molecule, Gt, Gg, Gg', Tt, and Tg, have been unambiguously assigned. Over 6700 lines of the Gt, Gg, and Gg' species, for quantum number values reaching K(a) = 33 and J = 67, were fitted in a joint analysis leading to the determination of DeltaE(Gg-Gt) = 47.82425(25) cm(-1) and DeltaE (Gg'-Gg) = 3.035047(11) cm(-1). Stark effect measurements in supersonic expansion were used to further confirm the assignment. The results are compared with those for the ethanol molecule and with ab initio calculations, allowing several inferences to be drawn concerning the differences in the large amplitude torsional potential of the hydroxyl group in the two molecules.

Differences between the features of invasive community-onset methicillin-resistant Staphylococcus aureus (cMRSA) and methicillin-susceptible S. aureus (cMSSA) infections are incompletely understood. Fifty-seven patients with invasive cMRSA infection were prospectively identified at two teaching hospitals; for each cMRSA case, two cases of invasive cMSSA infection acted as controls. The primary outcome was 30-day all-cause mortality. Patients with invasive cMRSA infection were more likely to be Aboriginal (25% vs. 14%, age-adjusted odds ratio [OR] 2.5, p = 0.037), reside in a long-term care facility and/or have been hospitalised in the previous year (51% vs. 34%, p = 0.04) and less likely to have endocarditis (2% vs. 12%, p = 0.02) or require admission to an intensive care unit or high-dependency area (7% vs. 21%, p = 0.02). All-cause mortality at 30 days was similar in the cMRSA and cMSSA groups (9% vs. 7%, p = 0.68). Panton-Valentine leukocidin (PVL) genes were detected in a similar proportion of cMRSA and cMSSA isolates (32% vs. 27%, p = 0.49) and the presence of PVL genes was associated with younger age (35 years vs. 55 years, p < 0.001), Aboriginal ethnicity (38% vs. 10%, p < 0.001), skin and soft-tissue infection (54% vs. 19%, p < 0.001), lower illness severity at presentation (SAPS II score 9 vs. 21, p = 0.001) and shorter hospitalisation (9 days vs. 24 days, p < 0.001). Patients with "PVL-positive" and "PVL-negative" S. aureus infection had similar 30-day all-cause mortality (4% vs. 9%, p = 0.28). Few clinical features differentiated patients with invasive cMRSA infection from those with infection caused by cMSSA. Invasive "PVL-positive" S. aureus infection was associated with less morbidity but similar mortality to "PVL-negative" infection.

Drosophila tracheal fusion cells play multiple important roles in guiding and facilitating tracheal branch fusion. Mechanistic understanding of how fusion cells function during development requires deciphering their transcriptional circuitry. In this paper, three genes with distinct patterns of fusion cell expression were dissected by transgenic analysis to identify the cis-regulatory modules that mediate their transcription. Bioinformatic analysis involving phylogenetic comparisons coupled with mutational experiments were employed. The dysfusion bHLH-PAS gene was shown to have two fusion cell cis-regulatory modules; one driving initial expression and another autoregulatory module to enhance later transcription. Mutational dissection of the early module identified at least four distinct inputs, and included putative binding sites for ETS and POU-homeodomain proteins. The ETS transcription factor Pointed mediates the transcriptional output of the branchless/breathless signaling pathway, suggesting that this pathway directly controls dysfusion expression. Fusion cell cis-regulatory modules of CG13196 and CG15252 require two Dysfusion:Tango binding sites, but additional sequences modulate the breadth of activation in different fusion cell classes. These results begin to decode the regulatory circuitry that guides transcriptional activation of genes required for fusion cell morphogenesis.

Clonal complex 59 (CC59) community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains were characterized using pulsed-field gel electrophoresis, spa typing, multilocus sequence typing, diagnostic DNA microarrays, and PCRs targeting staphylococcal cassette chromosome mec (SCCmec) elements and Panton-Valentine leukocidin (PVL). Six distinct groups within CC59 were characterized. At least seven different variants of SCCmec elements were identified (IVa [2B], IVb [2B], IVd [2B], IV variant [2B], IVa [2B&5], V variant [5C2], and V [5C2&5]). (The structural type is indicated by a Roman numeral, with a lowercase letter indicating the subtype, and the ccr complex and the mec complex are indicated by an Arabic numeral and an uppercase letter, respectively. Where there is an extra ccr element, this is indicated by "&" and an Arabic numeral designating the ccr type.) The first group is similar to the American sequence type 59 (ST59) MRSA-IV CA-MRSA strain USA1000. The second group includes a PVL-negative ST87 strain with an SCCmec element of subtype IVb (2B). The third group comprises PVL-variable ST59 MRSA-IV strains harboring multiple SCCmec IV subtypes. PVL-negative ST59 MRSA strains with multiple or composite SCCmec elements (IVa [2B&5]) form the fourth group. Group 5 corresponds to the internationally known "Taiwan clone," a PVL-positive strain with a variant SCCmec element (V [5C2&5]). This strain proved to be the most common CC59 MRSA strain isolated in Western Australia. Finally, group 6 encompasses the ST59 MRSA-V variant (5C2). The differentiation of CC59 into groups and strains indicates a rapid evolution and spread of SCCmec elements. Observed differences between groups of strains as well as intrastrain variability within a group facilitate the tracing of their spread.

Background: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N1)2009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection., Methodology/principal Findings: Patients with community-acquired pneumonia (CAP) caused by co-infection with pandemic A(H1N1)2009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N1)2009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL)., Conclusions/significance: Clinicians managing patients with pandemic A(H1N1)2009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic A( H1N1) 2009 influenzavirus co-infection.

The objective was to compare the epidemiology and outcome of healthcare- (HA-) and community-associated (CA-) MRSA bacteraemia. A 10-year retrospective study of MRSA bacteraemia was carried out. Episodes were classified according to established criteria. Molecular typing was performed on a subset of isolates. Of 197 MRSA bacteraemia episodes, 178 (90.4%) were classified as HA-MRSA and 19 (9.6%) as CA-MRSA. All-cause 7- and 30-day mortality rates were similar in the HA and CA-MRSA bacteraemia groups; however, 1-year mortality was higher in the HA-MRSA bacteraemia group (48.3% vs 21.1% [p = 0.023]). Thirty-day all-cause mortality was significantly lower if empiric antimicrobial therapy included agent(s) to which the isolate tested susceptible, compared with patients receiving "inactive" therapy (19% vs 35.1% [p = 0.011]). The majority of MRSA bacteraemia episodes were caused by clones known to circulate in the community. All-cause mortality is as high in HA- as in CA-MRSA bacteraemia. Thirty-day mortality was significantly reduced if the patient received an antibiotic with activity against the MRSA isolate.

Biennial community-based Staphylococcus aureus antimicrobial surveillance programs have been performed by the Australian Group for Antimicrobial Resistance (AGAR) since 2000. Over this time the percentage of S. aureus identified as methicillin resistant has increased significantly from 10.3% in 2000 to 16% in 2006. This increase has occurred throughout Australia and has been due to the emergence of community-associated MRSA (CA-MRSA) clones. However, healthcare associated MRSA were still predominant in New South Wales/Australian Capital Territory and Victoria/Tasmania. In the 2006 survey CA-MRSA accounted for 8.8% of community-onset S. aureus infections. Although multiple CA-MRSA clones were characterised, the predominate clone identified was Queensland (Qld) MRSA (ST93-MRSA-IV) a Panton-Valentine leukocidin (PVL) positive MRSA that was first reported in Queensland and northern New South Wales in 2003 but has now spread throughout Australia. Several international PVL-positive CA-MRSA clones were also identified including USA300 MRSA (ST8-MRSA-IV). In addition, PVL was detected in an EMRSA-15 (ST22-MRSA-IV) isolate; a hospital associated MRSA clone that is known to be highly transmissible in the healthcare setting. With the introduction of the international clones and the transmission of Qld MRSA throughout the country, over 50% of CA-MRSA in Australia are now PVL positive. This change in the epidemiology of CA-MRSA in the Australian community will potentially result in an increase in skin and soft tissue infections in young Australians. As infections caused by these strains frequently results in hospitalisation their emergence is a major health concern.

Wounds in Drosophila and mouse embryos induce similar genetic pathways to repair epidermal barriers. However, the transcription factors that transduce wound signals to repair epidermal barriers are largely unknown. We characterize the transcriptional regulatory enhancers of 4 genes-Ddc, ple, msn, and kkv-that are rapidly activated in epidermal cells surrounding wounds in late Drosophila embryos and early larvae. These epidermal wound enhancers all contain evolutionarily conserved sequences matching binding sites for JUN/FOS and GRH transcription factors, but vary widely in trans- and cis-requirements for these inputs and their binding sites. We propose that the combination of GRH and FOS is part of an ancient wound-response pathway still used in vertebrates and invertebrates, but that other mechanisms have evolved that result in similar transcriptional output. A common, but largely untested assumption of bioinformatic analyses of gene regulatory networks is that transcription units activated in the same spatial and temporal patterns will require the same cis-regulatory codes. Our results indicate that this is an overly simplistic view.

Objective: To describe an outbreak of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner., Setting: A medical practitioner's office and 4 hospitals in Perth, Western Australia., Patients: Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner., Methods: We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control audit of the medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner., Results: Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified., Conclusions: This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.

In 2005 the Australian Group for Antimicrobial Resistance (AGAR) conducted a survey of the prevalence of antimicrobial resistance in unique clinical isolates of Streptococcus pneumoniae. Twenty laboratories from the 5 mainland states and the Australian Capital Territory collected 1,776 isolates prospectively and tested them by disk diffusion, Etest and/or agar dilution against a range of antimicrobials. Data from this survey were compared with AGAR surveys conducted in 1989, 1994, 1999 and 2002. Non-susceptibility to penicillin was detected in 28.0% of isolates, 22.7% were erythromycin resistant, 15.6% clindamycin resistant, 18.4% tetracycline resistant and 31.0% trimethoprim-sulphamethoxazole resistant. Levofloxacin resistance was detected in only 4 of 1,775 (0.2%) isolates tested. Intermediate resistance to levofloxacin was detected in another 4 isolates. Moxifloxacin resistance was present in 2 isolates with minimum inhibitory concentrations of 3 mg/L and 4 mg/L. Seventeen point three per cent of isolates were multi-resistant (acquired resistance to more than 2 drug classes). Trend data show an increase in penicillin non-susceptible strains in each survey from 1989 to 2005. Between 1999 and 2005 the proportion of invasive strains with high-level resistance increased from 2.6% to 5.4%. After a rapid emergence and rise in resistance between 1989 and 1999, recent studies have documented a continuing rise in resistance to all non-beta-lactams except trimethoprim-sulphamethoxazole.

Antibiotic resistance in Enterococcus species causing clinical disease was examined in a point-prevalence study in 2005. Twenty-two sites around Australia collected up to 100 consecutive isolates and tested them for susceptibility to ampicillin, vancomycin, high-level gentamicin and/or high-level streptomycin using standardised methods. Results were compared to similar surveys conducted in 1995, 1999 and 2003. In the 2005 survey, Enterococcus faecalis (1,987 strains) and E. faecium (180 strains) made up 98.6% of the 2,197 isolates tested. Ampicillin resistance was common (77%) in E. faecium, but rare still in E. faecalis (0.2%). Resistance to vancomycin was 7.2% in E. faecium and 0.2% in E. faecalis; the vanB gene was detected in all vancomycin-resistant isolates. High-level resistance to gentamicin was 35.8% in E. faecalis and 52.2% in E. faecium; the figures for high-level streptomycin resistance were 10.3% and 60.2% respectively. Compared to previous Australian Group on Antimicrobial Resistance surveys in 1995, 1999 and 2003, the proportions of vancomycin resistance and high-level gentamicin resistance in enterococci are increasing. It is important to have an understanding of the occurrence of vancomycin resistant enterococci and high level aminoglycoside resistance in Australia to guide infection control practices, antibiotic prescribing policies and drug regulatory decisions.

The Australian Group for Antimicrobial Resistance conducted a survey of the prevalence of antimicrobial resistance in unique clinical isolates of Staphylococcus aureus from patients admitted to hospital for more than 48 hours. Thirty-two laboratories from all states and territories collected 2,908 isolates from 1 May 2005, of which 31.9% were methicillin-resistant Staphylococcus aureus (MRSA). The regional prevalence of MRSA varied significantly (P < 0.0001) from 22.5% in Western Australia to 43.4% in New South Wales/Australian Capital Territory. Prevalence of MRSA from individual laboratories varied even more from 4% to 58%. This variation was explained in part by distribution of age with the risk of MRSA significantly (P < 0.0001) increasing with age. Other unmeasured factors including hospital activity and infection control practices in the individual institution may have also contributed. Further investigation is warranted as reductions in prevalence would reduce morbidity, mortality and healthcare costs.

Objective: To describe the control of an outbreak of infection and colonization with the New York/Japan methicillin-resistant Staphylococcus aureus (MRSA) clone in multiple healthcare facilities, and to demonstrate the importance of making an MRSA management policy involving molecular typing of MRSA into a statewide public health responsibility., Setting: A range of healthcare facilities, including 2 metropolitan teaching hospitals and a regional hospital, as well as several community hospitals and long-term care facilities in a nonmetropolitan healthcare region., Interventions: A comprehensive, statewide MRSA epidemiological investigation and management policy., Results: In May 2005, there were 3 isolates referred to the Western Australian Gram-Positive Bacteria Typing and Research Unit that were identified as the New York/Japan MRSA clone, a pandemic MRSA clone with the ability to spread and replace existing clones in a region. Subsequent investigation identified 28 additional cases of infection and/or colonization dating from 2002 onward, including 1 involving a colonized healthcare worker (HCW) who had previously been hospitalized overseas. Of the 31 isolates detected, 25 were linked epidemiologically and via molecular typing to the isolate recovered from the colonized HCW. Four isolates appeared to have been introduced separately from overseas. Although the isolate from the single remaining case patient was genetically indistinct from the isolates that spread within Western Australia, no specific epidemiological link could be established. The application of standard outbreak management strategies reduced further spread., Conclusions: The elimination of the New/York Japan MRSA clone in a healthcare region demonstrates the importance of incorporating MRSA management policy into statewide public health programs. The mainstays of such programs should include a comprehensive and effective outbreak identification and management policy (including pre-employment screening of HCWs, where applicable) and MRSA clone identification by multilocus sequence typing.