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It has been claimed that the variability of field quasars resembles gravitational lensing by a large cosmological population of free-floating planets with mass |$\sim\!\! 10\ {\rm M}_{\oplus }$|⁠. However, Galactic photometric monitoring experiments, on the other hand, exclude a large population of such planetary-mass gravitational lenses. These apparently contradictory pieces of evidence can be reconciled if the objects under consideration have a mean column density that lies between the critical column densities for gravitational lensing in these two contexts. Dark matter in that form is known to be weakly collisional, so a core develops in galaxy halo density profiles, and a preferred model has already been established. Here, we consider what such a model implies for Q2237+0305, which is the best-studied example of a quasar that is strongly lensed by an intervening galaxy. We construct microlensing magnification maps appropriate to the four macro-images of the quasar – all of which are seen through the bulge of the galaxy. Each of these maps exhibits a caustic network arising from the stars, plus many small, isolated caustics arising from the free-floating 'planets' in the lens galaxy. The 'planets' have little influence on the magnification histograms but a large effect on the statistics of the magnification gradients. We compare our predictions to the published Optical Gravitational Lensing Experiment (OGLE) photometry of Q2237+0305 and find that these data are consistent with the presence of the hypothetical 'planets'. However, the evidence is relatively weak because the OGLE data set is not well suited to testing our predictions and requires low-pass filtering for this application. New data from a large, space-based telescope are desirable to address this issue. [ABSTRACT FROM AUTHOR]

Context: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear. Objective: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function. Methods: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. Results: β-cell function was 40% greater after WP (P = .001) and was accompanied with a −22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (−1.5 mmol/L and −16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). Conclusion: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation. Trial registry ISRCTN ID: ISRCTN17563146 [ABSTRACT FROM AUTHOR]

A pulsar dynamic spectrum is an inline digital hologram of the interstellar medium; it encodes information on the propagation paths by which signals have travelled from source to telescope. To decode the hologram, it is necessary to 'retrieve' the phases of the wavefield from intensity measurements, which directly gauge only the field modulus, by imposing additional constraints on the model. We present a new method for phase retrieval in the context of pulsar spectroscopy. Our method makes use of the Fast Iterative Shrinkage Thresholding Algorithm (FISTA) to obtain sparse models of the wavefield in a hierarchical approach with progressively increasing depth. Once the tail of the noise distribution is reached the hierarchy terminates with a final, unregularized optimization. The result is a fully dense model of the complex wavefield that permits the discovery of faint signals by appropriate averaging. We illustrate the performance of our method on synthetic test cases and on real data. Our algorithm, which we call H-FISTA, is implemented in the python programming language and is freely available. [ABSTRACT FROM AUTHOR]

We study the influence of a cosmological population of dense gas clouds on distant sources, with an emphasis on quasar optical variability. In addition to gravitational lensing, such clouds affect flux measurements via refraction in the neutral gas and via dust extinction, leading to a variety of possible light curves even in the low optical depth limit. We classify and illustrate the types of light curves that can arise. For sources as large as quasars, we show that gravitational lensing and extinction are the dominant effects, with gas refraction playing only a minor role. We find that clouds with mass |$\sim 10^{-4.5\pm 0.5}\, \mathrm{M}_\odot$| can reproduce the observed distribution of quasar variation amplitudes, but only if such clouds make up a large fraction of the closure density. In that case, there may also be substantial extinction of distant optical sources, which can, in principle, be constrained by data on 'standard candles' such as type Ia supernovae. Unfortunately, that extinction is essentially grey, even when the material opacity is strongly wavelength dependent, making it difficult to distinguish from the influence of the background geometry. We propose a novel statistical test of the origin of quasar variability, based on the angular structure of the variation timescale for a large number of quasars distributed all over the sky. If quasar variability is primarily due to nanolensing, then angular structure is expected to include a quadrupole term of amplitude |$\sim 5{{\ \rm per\ cent}}$|⁠ , which ought to be measurable with future data from the Gaia mission. [ABSTRACT FROM AUTHOR]

We discovered rapid intra-day variability in radio source PMN J1726+0639 at GHz frequencies, during a survey to search for such variability with the Australia Telescope Compact Array. Follow-up observations were conducted over 2 yr and revealed a clear, repeating annual cycle in the rate, or characteristic time-scale, of variability, showing that the observed variations can be attributed to scintillations from interstellar plasma inhomogeneities. The strong annual cycle includes an apparent 'standstill' in April and another in September. We fit kinematic models to the data, allowing for finite anisotropy in the scintillation pattern. The cycle implies a very high degree of anisotropy, with an axial ratio of at least 13:1, and the fit is consistent with a purely one-dimensional scintillation pattern. The position angle of the anisotropy, and the transverse velocity component are tightly constrained. The parameters are inconsistent with expectations from a previously proposed model of scattering associated with plasma filaments radially oriented around hot stars. We note that evidence for a foreground interstellar cloud causing anomalous Ca  ii absorption towards the nearby star Rasalhague (α Oph) has been previously reported, and we speculate that the interstellar scintillation of PMN J1726+0639 might be associated with this nearby cloud. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases are a group of common inherited diseases causing disruption of oxidative phosphorylation. Some patients with mitochondrial disease have endocrine manifestations, with diabetes mellitus being predominant but also include hypogonadism, hypoadrenalism, and hypoparathyroidism. There have been major developments in mitochondrial disease over the past decade that have major implications for all patients. The collection of large cohorts of patients has better defined the phenotype of mitochondrial diseases and the majority of patients with endocrine abnormalities have involvement of several other systems. This means that patients with mitochondrial disease and endocrine manifestations need specialist follow-up because some of the other manifestations, such as stroke-like episodes and cardiomyopathy, are potentially life threatening. Also, the development and follow-up of large cohorts of patients means that there are clinical guidelines for the management of patients with mitochondrial disease. There is also considerable research activity to identify novel therapies for the treatment of mitochondrial disease. The revolution in genetics, with the introduction of next-generation sequencing, has made genetic testing more available and establishing a precise genetic diagnosis is important because it will affect the risk for involvement for different organ systems. Establishing a genetic diagnosis is also crucial because important reproductive options have been developed that will prevent the transmission of mitochondrial disease because of mitochondrial DNA variants to the next generation. [ABSTRACT FROM AUTHOR]

Background: Neisseria gonorrhoeae is a Gram-negative bacterial pathogen that causes gonorrhoea. No vaccine is available to prevent gonorrhoea and the emergence of MDR N. gonorrhoeae strains represents an immediate public health threat.Objectives: To evaluate whether PBT2/zinc may sensitize MDR N. gonorrhoeae to natural cationic antimicrobial peptides.Methods: MDR strains that contain differing resistance mechanisms against numerous antibiotics were tested in MIC assays. MIC assays were performed using the broth microdilution method according to CLSI guidelines in a microtitre plate. Serially diluted LL-37 or PG-1 was tested in combination with a sub-inhibitory concentration of PBT2/zinc. Serially diluted tetracycline was also tested with sub-inhibitory concentrations of PBT2/zinc and LL-37. SWATH-MS proteomic analysis of N. gonorrhoeae treated with PBT2/zinc, LL-37 and/or tetracycline was performed to determine the mechanism(s) of N. gonorrhoeae susceptibility to antibiotics and peptides.Results: Sub-inhibitory concentrations of LL-37 and PBT2/zinc synergized to render strain WHO-Z susceptible to tetracycline, whereas the killing effect of PG-1 and PBT2/zinc was additive. SWATH-MS proteomic analysis suggested that PBT2/zinc most likely leads to a loss of membrane integrity and increased protein misfolding and, in turn, results in bacterial death.Conclusions: Here we show that PBT2, a candidate Alzheimer's and Huntington's disease drug, can be repurposed to render MDR N. gonorrhoeae more susceptible to the endogenous antimicrobial peptides LL-37 and PG-1. In the presence of LL-37, PBT2/zinc can synergize with tetracycline to restore tetracycline susceptibility to gonococci resistant to this antibiotic. [ABSTRACT FROM AUTHOR]

Following corporate spinoffs, unit boards are formed from scratch. We find that these "de novo" boards are smaller, more independent, include more outside directors with relevant industry expertise, and derive more industry expertise from outsiders than do industryand size-matched peers. These differences are observed only when the unit CEO was not the CEO or a director of the pre-spinoff parent firm--that is, when there is a greater need to assess the CEO's ability and match with the firm. We conclude that the need for CEO assessment is an important element of the structure of newly formed boards. [ABSTRACT FROM AUTHOR]

We present the results from an Australian Square Kilometre Array Pathfinder search for radio variables on timescales of hours. We conducted an untargeted search over a 30 deg2 field, with multiple 10-h observations separated by days to months, at a central frequency of 945 MHz. We discovered six rapid scintillators from 15-min model-subtracted images with sensitivity of |$\sim\! 200\, \mu$| Jy/beam; two of them are extreme intra-hour variables with modulation indices up to |$\sim 40{{\ \rm per\ cent}}$| and timescales as short as tens of minutes. Five of the variables are in a linear arrangement on the sky with angular width ∼1 arcmin and length ∼2 degrees, revealing the existence of a huge plasma filament in front of them. We derived kinematic models of this plasma from the annual modulation of the scintillation rate of our sources, and we estimated its likely physical properties: a distance of ∼4 pc and length of ∼0.1 pc. The characteristics we observe for the scattering screen are incompatible with published suggestions for the origin of intra-hour variability leading us to propose a new picture in which the underlying phenomenon is a cold tidal stream. This is the first time that multiple scintillators have been detected behind the same plasma screen, giving direct insight into the geometry of the scattering medium responsible for enhanced scintillation. [ABSTRACT FROM AUTHOR]

PKS B1322–110 is a radio quasar that is located only 8 |$.^\prime$| 5 in angular separation from the bright B star Spica. It exhibits intraday variability in its flux density at GHz frequencies attributed to scintillations from plasma inhomogeneities. We have tracked the rate of scintillation of this source for over a year with the Australia Telescope Compact Array, recording a strong annual cycle that includes a near-standstill in August and another in December. The cycle is consistent with scattering by highly anisotropic plasma microstructure, and we fit our data to that model in order to determine the kinematic parameters of the plasma. Because of the low-ecliptic latitude of PKS B1322–110 , the orientation of the plasma microstructure is poorly constrained. None the less at each possible orientation our data single out a narrow range of the corresponding velocity component, leading to a one-dimensional constraint in a two-dimensional parameter space. The constrained region is consistent with a published model in which the scattering material is associated with Spica and consists of filaments that are radially oriented around the star. This result has a 1 per cent probability of arising by chance. [ABSTRACT FROM AUTHOR]

Herschel observations of far-infrared N+emission lines have demonstrated that dense plasma, with |$n_\mathrm{ e}\sim 30\, {\rm cm^{-3}}$|⁠, is ubiquitous in the inner Galactic plane. By combining the information from Herschel with other tracers of ionized gas, we build a picture of this dense plasma. We adopt a collisional ionization model, so the analysis is not tied to a specific energization mechanism. We find that the dense plasma is concentrated in a disc that is 130 pc thick and makes a significant contribution to radio pulsar dispersion measures in the inner Galactic plane. The strength of the far-infrared N+emission requires high temperatures in the plasma, with |$T \simeq 19\,000\, {\rm K}$| indicated both by the ratio of N+to C+, and by the ratio of N+to microwave bremsstrahlung in the inner Galactic plane. This parallels the situation at high Galactic latitudes, where strong optical emission is observed from N+(and S+), relative to both H α and microwave bremsstrahlung, and suggests a common origin. If so, the same gas provides a natural explanation for the extreme radio-wave scattering phenomena that are sometimes observed in pulsars and quasars. We therefore propose a new picture of the warm ionized medium as seen in emission, in which the plasma is dense, hot, and localized in numerous structures of size |${\sim } 10^2\, {\rm au}$| that are clustered around stars. [ABSTRACT FROM AUTHOR]

Study Question: How is endometriosis associated with adverse maternal, fetal and neonatal outcomes of pregnancy?Summary Answer: Women with endometriosis are at elevated risk for serious and important adverse maternal (pre-eclampsia, gestational diabetes, placenta praevia and Cesarean section) and fetal or neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth and neonatal death).What Is Known Already: A number of studies have shown an association between endometriosis and certain adverse maternal and fetal outcomes, but the results have been conflicting with potential for confounding by the use of assisted reproductive technology.Study Design, Size, Duration: A systematic review and meta-analysis of observational studies (1 January 1990-31 December 2017) that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted.Participants/materials, Setting, Methods: Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies; included women greater than 20 weeks gestational age with endometriosis; included a control group of gravid women without endometriosis; and, reported at least one of the outcomes of interest. Each study was reviewed for inclusion, data were extracted and risk of bias was assessed by two independent reviewers.Main Results and the Role Of Chance: The search strategy identified 33 studies (sample size, n = 3 280 488) for inclusion. Compared with women without endometriosis, women with endometriosis had higher odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01-1.39]), gestational hypertension and/or pre-eclampsia (OR = 1.21 [1.05-1.39]), gestational diabetes (OR = 1.26 [1.03-1.55]), gestational cholestasis (OR = 4.87 [1.85-12.83]), placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38-2.07]), antepartum hospital admissions (OR = 3.18 [2.60-3.87]), malpresentation (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04-2.01]) and cesarean section (OR = 1.86 [1.51-2.29]). Fetuses and neonates of women with endometriosis were also more likely to have preterm premature rupture of membranes (OR = 2.33 [1.39-3.90]), preterm birth (OR = 1.70 [1.40-2.06]), small for gestational age <10th% (OR = 1.28 [1.11-1.49]), NICU admission (OR = 1.39 [1.08-1.78]), stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46-2.16]). Among the subgroup of women who conceived spontaneously, endometriosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight. Among the subgroup of women who conceived with the use of assisted reproductive technology, endometriosis was found to be associated with placenta praevia and preterm birth.Limitations, Reasons For Caution: As with any systematic review, the review is limited by the quality of the included studies. The diagnosis for endometriosis and the selection of comparison groups were not uniform across studies. However, the effect of potential misclassification would be bias towards the null hypothesis.Wider Implications Of the Findings: The association between endometriosis with the important and serious pregnancy outcomes observed in our meta-analysis, in particular stillbirth and neonatal death, is concerning and warrants further studies to elucidate the mechanisms for the observed findings.Study Funding/competing Interest(s): Dr Shifana Lalani is supported by a Physicians' Services Incorporated Foundation Research Grant, and Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services. Dr Singh declares conflicts of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors have no conflicts of interests to declare.Registration Number: PROSPERO CRD42015013911. [ABSTRACT FROM AUTHOR]

M and M-like surface proteins from group A Streptococcus (GAS) act as virulence factors and have been used in multiple vaccine candidates. While the M protein has been extensively studied, the two genetically and functionally related M-like proteins, Mrp and Enn, although present in most streptococcal strains have been relatively less characterised. We compile the current state of knowledge for these two proteins, from discovery to recent studies on function and immunogenicity, using the M protein for comparison as a prototype of this family of proteins. We focus on the known interactions between M-like proteins and host ligand proteins, and analyse the genetic data supporting these interactions. We discuss known and possible functions of M-like proteins during GAS infections, and highlight knowledge gaps where further investigation is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Streptococcus pyogenes, the Group A Streptococcus (GAS), is the most common cause of bacterial pharyngitis in children and adults. Innate and adaptive host immune responses are fundamental for defense against streptococcal pharyngitis and are central to the clinical manifestation of disease. Host immune responses also contribute to the severe poststreptococcal immune diseases that constitute the major disease burden for this organism. However, until recently, little was known about the host responses elicited during infection. Cellular mediators of innate immunity used during host defense against GAS include epithelial cells, neutrophils, macrophages, and dendritic cells (DCs), which are reported to secrete a number of soluble inflammatory mediators, such as antimicrobial peptides (AMPs); eicosanoids, including PGE2 and leukotriene B4 (LTB4); chemokines; and proinflammatory cytokines. Th1 and Th17 responses play significant roles in adaptive immunity in both murine models of GAS pharyngitis and in human tonsil tissue. A number of inflammatory complications are associated with GAS pharyngitis, which can lead to chronic disease in patients. These include scarlet fever, tonsillar hypertrophy, and sleep apnea, as well as postinfectious sequelae, such as acute rheumatic fever (ARF), poststreptococcal glomerulonephritis, and guttate psoriasis (GP). This review aims to present the current state of knowledge on innate and adaptive immune responses elicited during GAS pharyngitis, mechanisms by which GAS evades these responses, the emerging role of the pharyngeal microbiota, and how the interplay among these factors can influence the outcome of infection and inflammation‐related complications. [ABSTRACT FROM AUTHOR]

Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958.Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli. [ABSTRACT FROM AUTHOR]

We report radio observations of the quasar PMN J1106-3647. Our data, taken with the Australia Telescope Compact Array, show large variations in the amplitude and shape of its spectrum, on a short time-scale. A great variety of spectral features is evident, including sharp kinks, broad spectral peaks and wiggles. No two spectra are alike. We interpret the variations as interstellar scintillation of a radio source that is compact, but not point-like. Under this interpretation, complex spectral structure can arise purely refractively, under high magnification conditions, or from interference between waves that have been scattered by small-scale density fluctuations (diffractive scintillation). Both effects may be playing a role in J1106-3647, and we tentatively identify kinks with the former, and wiggles with the latter. Diffractive scintillation of active galactic nuclei is uncommon, as the fringe visibility is low for all but the most compact radio sources. Refractive interpretation of the kink implies that the source has a sharp, concave boundary. Our data are consistent with a mildly boosted synchrotron source, provided the scattering material is at a distance ~50 pc from us. [ABSTRACT FROM AUTHOR]

BACKGROUND Population-level sociologic studies have suggested that adverse societal conditions may affect fetal viability in a sex-specific manner and thereby modify the ratio of male vs. female babies. This concept suggests that there may exist certain physiologic features in a woman that relate to her likelihood of delivering a boy or girl. We thus established a preconception cohort to prospectively evaluate the relationship between maternal pregravid health and sex of the baby. METHODS In this analysis nested within an observational cohort study, 1,411 newly married women in Liuyang, China, underwent pregravid cardiometabolic characterization (including anthropometry and measurement of blood pressure, cholesterol, triglycerides, and glucose) at median 26.3 weeks before a singleton pregnancy, delivering at 39.0 ± 1.3 weeks gestation. RESULTS Systolic blood pressure before pregnancy was higher in women who delivered a boy than in those who had a girl (112.5 ± 11.9 vs. 109.6 ± 12.0 mm Hg, P < 0.0001). The prevalence of a male baby progressively increased across quintiles of pregravid systolic blood pressure (P < 0.0001). After covariate adjustment, mean adjusted pregravid systolic blood pressure was higher in mothers of boys vs. girls (106.0 vs. 103.3 mm Hg, P = 0.0015). On logistic regression analysis, pregravid systolic blood pressure emerged as the only significant predictor of having a male baby (adjusted odds ratio = 1.017 per mm Hg, 95% confidence interval = 1.007-1.028). The pregravid difference in blood pressure between mothers of boys and girls was not present during any trimester of pregnancy. CONCLUSION Maternal blood pressure before pregnancy is a previously unrecognized factor that may be associated with the likelihood of delivering a boy or girl. [ABSTRACT FROM AUTHOR]

Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing scarlet fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 scarlet fever isolate related to United Kingdom outbreak strains. National surveillance to monitor this pandemic is recommended. [ABSTRACT FROM AUTHOR]

Summary We present an updated version of our computational pipeline, PathSeq, for the discovery and identification of microbial sequences in genomic and transcriptomic libraries from eukaryotic hosts. This pipeline is available in the Genome Analysis Toolkit (GATK) as a suite of configurable tools that can report the microbial composition of DNA or RNA short-read sequencing samples and identify unknown sequences for downstream assembly of novel organisms. GATK PathSeq enables sample analysis in minutes at low cost. In addition, these tools are built with the GATK engine and Apache Spark framework, providing robust, rapid parallelization of read quality filtering, host subtraction and microbial alignment in workstation, cluster and cloud environments. Availability and implementation These tools are available as a part of the GATK at https://github.com/broadinstitute/gatk. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

The amino acid glutamate is a major metabolic hub in many organisms and as such is involved in diverse processes in addition to its role in protein synthesis. Nitrogen assimilation, nucleotide, amino acid, and cofactor biosynthesis, as well as secondary natural product formation all utilize glutamate in some manner. Glutamate also plays a role in the catabolism of certain amines. Understanding glutamate's role in these various processes can aid in genome mining for novel metabolic pathways or the engineering of pathways for bioremediation or chemical production of valuable compounds. [ABSTRACT FROM AUTHOR]

Methylglyoxal is a dicarbonyl compound that acts as a toxic electrophile in biological systems. Methylglyoxal is produced in certain bacteria as a byproduct of glycolysis through methylglyoxal synthase. Like many bacteria, Group A Streptococcus (GAS), a Gram-positive human pathogen responsible for a wide spectrum of diseases, uses a two-step glyoxalase system to remove methylglyoxal. However, bioinformatic analysis revealed that no homologue of methylglyoxal synthase is present in GAS, suggesting that the role of the glyoxalase system is to detoxify methylglyoxal produced by the host. In this study, we investigated the role of methylglyoxal detoxification in the pathogenesis of GAS. A mutant (5448ΔgloA), deficient in glyoxylase I (S-lactoylglutathione lyase), was constructed and tested for susceptibility to methylglyoxal, human neutrophil survival and virulence in a murine model of infection. 5448ΔgloA was more sensitive to methylglyoxal and was also more susceptible to human neutrophil killing. Inhibition of neutrophil myeloperoxidase rescued the gloA-deficient mutant indicating that this enzyme was required for methylglyoxal production. Furthermore, the 5448ΔgloA mutant was slower at disseminating into the blood in the murine model. These data suggest that neutrophils produce methylglyoxal as an antimicrobial agent during bacterial infection, and the glyoxalase system is part of the GAS defence against the innate immune system during pathogenesis. [ABSTRACT FROM AUTHOR]

Background. Two proven nosocomial cases of Legionella pneumonia occurred at the Wesley Hospital (Brisbane, Australia) in May 2013. To trace the epidemiology of these cases, whole genome sequence analysis was performed on Legionella pneumophila isolates from the infected patients, prospective isolates collected from the hospital water distribution system (WDS), and retrospective patient isolates available from the Wesley Hospital and other local hospitals. Methods. Legionella pneumophila serogroup 1 isolates were cultured from patient sputum (n = 3), endobronchial washings (n = 3), pleural fluid (n = 1), and theWesley Hospital WDS (n = 39). Whole genome sequencing and de novo assembly allowed comparison with the L. pneumophila Paris reference strain to infer phylogenetic and epidemiological relationships. Rapid disinfection of the hospital WDS with a chlorinated, alkaline detergent and subsequent superchlorination followed by maintenance of residual free chlorine, combined with removal of redundant plumbing, was instituted. Results. The 2011 and 2013 L. pneumophila patient isolates were serogroup 1 and closely related to all 2013 hospital water isolates based on single nucleotide polymorphisms and mobile genetic element profiles, suggesting a single L. pneumophila population as the source of nosocomial infection. The L. pneumophila population has evolved to comprise 3 clonal variants, each associated with different parts of the hospital WDS. Conclusions. This study provides an exemplar for the use of clinical and genomic epidemiological methods together with a program of rapid, effective remedial biofilm, plumbing and water treatment to characterize and eliminate a L. pneumophila population responsible for nosocomial infections. [ABSTRACT FROM AUTHOR]

We report laboratory measurements of the absorption coefficient of solid para-H2, within the wavelength range from 1 to 16.7 μm, at high spectral resolution. In addition to the narrow rovibrational lines of H2 which are familiar from gas-phase spectroscopy, the data manifest double transitions and broad phonon branches that are characteristic specifically of hydrogen in the solid phase. These transitions are of interest because they provide a spectral signature which is independent of the impurity content of the matrix. We have used our data, in combination with a model of the ultraviolet absorptions of the H2 molecule, to construct the dielectric function of solid para-H2 over a broad range of frequencies. Our results will be useful in determining the electromagnetic response of small particles of solid hydrogen. The dielectric function makes it clear that pure H2 dust would contribute to infrared (IR) extinction predominantly by scattering starlight, rather than absorbing it, and the characteristic IR absorption spectrum of the hydrogen matrix itself will be difficult to observe. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development. [ABSTRACT FROM AUTHOR]

Background. Zinc plays an important role in human immunity, and it is known that zinc deficiency in the host is linked to increased susceptibility to bacterial infection. In this study, we investigate the role of zinc efflux in the pathogenesis of Streptococcus pyogenes (group A Streptococcus [GAS]), a human pathogen responsible for superficial infections, such as pharyngitis and impetigo, and severe invasive infections. Methods. The clinically important M1T1 wild-type strain was used in this study, and isogenic mutants were constructed with deletions in the czcD gene (Spy0653; which encodes a putative zinc efflux pump) and adjacent gczA gene (Spy0654; which encodes a putative zinc-dependent activator of czcD). Wild-type, isogenic mutants and complemented strains were tested for resistance against zinc stress, intracellular zinc accumulation, and virulence. Results. Both czcD and gczA mutants exhibited increased sensitivity to zinc. Transcriptional analyses indicate that GczA upregulates czcD in response to zinc. Both mutants displayed increased susceptibility to human neutrophil killing and reduced virulence in a murine infection model. Furthermore, we showed that neutrophils mobilize zinc in response to GAS. Conclusions. These data indicate that the innate immune system may use zinc as an antimicrobial agent and that zinc efflux is an important contributor to GAS pathogenesis. [ABSTRACT FROM AUTHOR]

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Comparative effectiveness research (CER) can assist patients, clinicians, purchasers, and policy makers in making more informed decisions that will improve cancer care and outcomes. Despite its promise, the factors that distinguish CER from other types of evidence remain mysterious to many oncologists. One concern is whether CER studies will improve decision making in oncology or only add to the massive amount of research information that decision makers must sift through as part of their professional responsibilities. In this report, we highlight several issues that distinguish CER from the most common way evidence is generated for cancer therapy- phase I-III clinical trials. To identify the issues that are most relevant to busy decision makers,we assembled a panel of active professionals with a wide range of roles in cancer care delivery. This panel identified five themes that they considered most important for CER in oncology, as well as fundamental threats to the validity of individual CER studies-threats they termed the "kiss of death" for their applicability to practice. In discussing these concepts,we also touched upon the notion of whether cancer is special among health issues with regard to how evidence is generated and used. The Oncologist 2013;18: 760-767 [ABSTRACT FROM AUTHOR]

Customized birth weight percentiles are weight-for-gestational-age percentiles that account for the influence of maternal characteristics on fetal growth. Although intuitively appealing, the incremental value they provide in the identification of intrauterine growth restriction (IUGR) over conventional birth weight percentiles is controversial. The objective of this study was to assess the value of customized birth weight percentiles in a simulated cohort of 100,000 infants aged 37 weeks whose IUGR status was known. A cohort of infants with a range of healthy birth weights was first simulated on the basis of the distributions of maternal/fetal characteristics observed in births at the Royal Victoria Hospital in Montreal, Canada, between 2000 and 2006. The occurrence of IUGR was re-created by reducing the observed birth weights of a small percentage of these infants. The value of customized percentiles was assessed by calculating true and false positive rates. Customizing birth weight percentiles for maternal characteristics added very little information to the identification of IUGR beyond that obtained from conventional weight-for-gestational-age percentiles (true positive rates of 61.8% and 61.1%, respectively, and false positive rates of 7.9% and 8.5%, respectively). For the process of customization to be worthwhile, maternal characteristics in the customization model were shown through simulation to require an unrealistically strong association with birth weight. [ABSTRACT FROM PUBLISHER]

The article focuses on a study which demonstrates the parasitism of common swift louse fly, Crataerina pallida. It is stated that the louse fly belongs to the family Hippoboscidae and is a parasite of the Common Swift, Apus Apus. The study revealed the life cycle of parasite which consists of larva, pupa and an adult and does not show any pathogenic effect on A. apus.

Medical devices provide an ecological niche for microbes to flourish as a biofilm community, protected from antimicrobials and host defenses. Biofilms formed by Candida albicans, the most common fungal pathogen, survive exposure to extraordinarily high drug concentrations. Here, we show that ß-glucan synthase Fks1p produces glucan, which is deposited in the biofilm matrix. The extracellular glucan is required for biofilm resistance and acts by sequestering antifungals, rendering cells resistant to their action. These findings provide the genetic basis for how biofilm matrix production governs drug resistance by impeding drug diffusion and also identify a useful biofilm drug target. [ABSTRACT FROM AUTHOR]

Background: Explicit patient consent requirements in privacy laws can have a negative impact on health research, leading to selection bias and reduced recruitment. Often legislative requirements to obtain consent are waived if the information collected or disclosed is de-identified. Objective: The authors developed and empirically evaluated a new globally optimal de-identification algorithm that satisfies the k-anonymity criterion and that is suitable for health datasets. Design: Authors compared OLA (Optimal Lattice Anonymization) empirically to three existing k-anonymity algorithms, Datafly, Samarati, and Incognito, on six public, hospital, and registry datasets for different values of k and suppression limits. Measurement: Three information loss metrics were used for the comparison: precision, discernability metric, and non-uniform entropy. Each algorithm's performance speed was also evaluated. Results: The Datafly and Samarati algorithms had higher information loss than OLA and Incognito; OLA was consistently faster than Incognito in finding the globally optimal de-identification solution. Conclusions: For the de-identification of health datasets, OLA is an improvement on existing k-anonymity algorithms in terms of information loss and performance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about reasons for variation in urinary catheterization prevalence in care homes.

The Australia Telescope 20-GHz (AT20G) Survey is a blind survey of the whole southern sky at 20 GHz (with follow-up observations at 4.8 and 8.6 GHz) carried out with the Australia Telescope Compact Array from 2004 to 2007. The Bright Source Sample (BSS) is a complete flux-limited subsample of the AT20G Survey catalogue comprising 320 extragalactic ) radio sources south of with Jy. Of these, 218 have near simultaneous observations at 8 and 5 GHz. In this paper we present an analysis of radio spectral properties in total intensity and polarization, size, optical identifications and redshift distribution of the BSS sources. The analysis of the spectral behaviour shows spectral curvature in most sources with spectral steepening that increases at higher frequencies (the median spectral index α, assuming , decreases from between 4.8 and 8.6 GHz to between 8.6 and 20 GHz), even if the sample is dominated by flat spectra sources (85 per cent of the sample has . The almost simultaneous spectra in total intensity and polarization allowed us a comparison of the polarized and total intensity spectra: polarized fraction slightly increases with frequency, but the shapes of the spectra have little correlation. Optical identifications provided an estimation of redshift for 186 sources with a median value of 1.20 and 0.13, respectively, for QSO and galaxies. [ABSTRACT FROM AUTHOR]

Aims: The ADIPOQ gene encodes the protein adiponectin, and decreased circulating adiponectin levels have been observed in cardiovascular disease. We investigated the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G-11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid artery intima media thickness (IMT) in a cohort of healthy subjects participating in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study. [ABSTRACT FROM PUBLISHER]

We present some first results on the variability, polarization and general properties of radio sources selected at 20 GHz, the highest frequency at which a sensitive radio survey has been carried out over a large area of sky. Sources with flux densities above 100 mJy in the Australia Telescope Compact Array 20 GHz pilot survey at declination −60° to −70° were observed at up to three epochs during 2002–04, including near-simultaneous measurements at 5, 8 and 18 GHz in 2003. Of the 173 sources detected, 65 per cent are candidate QSOs or BL Lac objects, 20 per cent galaxies and 15 per cent faint optical objects or blank fields. On a 1–2 yr time-scale, the general level of variability at 20 GHz appears to be low. For the 108 sources with good-quality measurements in both 2003 and 2004, the median variability index at 20 GHz was 6.9 per cent and only five sources varied by more than 30 per cent in flux density. Most sources in our sample show low levels of linear polarization (typically 1–5 per cent), with a median fractional polarization of 2.3 per cent at 20 GHz. There is a trend for fainter 20 GHz sources to have higher fractional polarization. At least 40 per cent of sources selected at 20 GHz have strong spectral curvature over the frequency range 1–20 GHz. We use a radio ‘two-colour diagram’ to characterize the radio spectra of our sample, and confirm that the flux densities of radio sources at 20 GHz (which are also the foreground point-source population for cosmic microwave background anisotropy experiments like Wilkinson Microwave Anisotropy Probe and Planck) cannot be reliably predicted by extrapolating from surveys at lower frequencies. As a result, direct selection at 20 GHz appears to be a more efficient way of identifying 90 GHz phase calibrators for Atacama Large Millimeter Array (ALMA) than the currently proposed technique of extrapolation from radio surveys at 1–5 GHz. [ABSTRACT FROM AUTHOR]

Background: Social support is, in general, positively associated with exercise behavior. However, social influence may not always be helpful and may sometimes lead to obligation or a sense of intrusion rather than encouragement or assistance. Purpose: The objective was to determine relationships among different types of social influence (social encouragement and social constraint) and exercise motivation and exercise behavior. Method: Structural equation modeling was used to investigate relationships among exercise and social influence variables. Results: A model was found to fit the data well in which social encouragement had an indirect association with exercise behavior through motivational variables. Social constraint was associated with only one aspect of exercise motivation-"have to," or obligatory, commitment-and had no direct or indirect association with exercise behavior. Conclusions: These findings emphasize the importance of social influences that promote desirable behaviors in contrast to those that pose constraints on the failure to perform desirable behaviors. [ABSTRACT FROM AUTHOR]

As a pilot study for the first all-sky radio survey at short wavelengths, we have observed 1216 deg2 of the southern sky at 18 GHz (16 mm) using a novel wide-band (3.4-GHz bandwidth) analogue correlator on one baseline of the Australia Telescope Compact Array. We scanned a region of sky between declination−71° and−59° with an rms noise level of 15 mJy. Follow-up radio imaging of candidate sources above a 4σ detection limit of 60 mJy resulted in 221 confirmed detections, for which we have measured accurate positions and flux densities. For extragalactic sources, the survey is roughly 70 per cent complete at a flux density of 126 mJy and 95 per cent complete above 300 mJy. Almost half the detected sources lie within a few degrees of the Galactic plane, but there are 123 sources with, which can be assumed to be extragalactic. The differential source counts for extragalactic sources in the rangeare well fitted by a relation of the form, in good agreement with the 15-GHz counts published by Taylor et al. and Waldram et al. Over 70 per cent of the extragalactic sources have a flat radio spectrum, and 29 per cent have inverted radio spectra. The optical identification rate is high: 51 per cent of the extragalactic sources are identified with stellar objects (candidate quasi-stellar objects), 22 per cent with galaxies and only 27 per cent with faint optical objects or blank fields. [ABSTRACT FROM AUTHOR]

We have measured 21-cm absorption spectra in the direction of three southern pulsars, PSRs B0736-40, B1451-68 and B1641-45, in three separate epochs spread over 2.5 yr. We see no evidence for any changes in the absorption spectra over this time span in spite of good velocity resolution and sensitivity. Towards PSR B 1641-45 we place an upper limit of 10[sup 19] cm[sup -2] on the change in the column density of the cold, neutral gas. In addition, we observed PSR B 1557-50 and compared its H I absorption spectrum with spectra taken in 1980 and 1994. A prominent deep absorption feature seen at -110 km s[sup -1] in 1994 is weaker in 2000 and likely was not present at all in 1980. Using the standard interpretation which links the distance traversed by the pulsar to a physical cloud size, this results in a cloud size of ∼1000 au and density of 2 × 10[sup 4] cm[sup -3], parameters typical of those seen in other observations. These results are also consistent with an alternative model by Deshpande who expects the largest variations in optical depth to be seen against the longest time intervals. [ABSTRACT FROM AUTHOR]

We have constructed an aromatic amino acid auxotrophic mutant of Bordetella bronchiseptica, harbouring mutations in aroA and trpE to investigate the use of such a strain as a live-attenuated vaccine. B. bronchiseptica aroA trpE was unable to grow in minimal medium without aromatic supplementation. Compared to the parental wild-type strain, the mutant displayed significantly reduced abilities to invade and survive within the mouse macrophage-like cell line J774A.1 in vitro and in the murine respiratory tract following experimental intranasal infection. Mice vaccinated with B. bronchiseptica aroA trpE displayed significant dose-dependent increases in B. bronchiseptica-specific antibody responses, and exhibited increases in the number of B. bronchiseptica-reactive spleen cells in lymphoproliferation assays. Immunised animals were protected against lung colonisation after challenge with the wild-type parental strain. With such a broad host range displayed by B. bronchiseptica, the attenuated strain constructed in this study may not only be used for the prevention of B. bronchiseptica-associated disease, but also for the potential delivery of heterologous antigen. [Copyright &y& Elsevier]

Introduction: Research indicates that military service involves stressors that may be related to depression. However, the military provides financial, educational, psychological, and social advantages that may help to mitigate the effects of service-related stressors. Because most prior research was based on cross-sectional data or small clinical samples, we explored individual-level trajectories of depression over time.Methods: Data came from the restricted-use version of the National Longitudinal Study of Adolescent to Adult Health (Add Health) in four survey waves from 1994 to 2008, with a total of 1,112 service members, of whom 231 were female, and a total sample size of 13,544. Statistical estimation employed the multilevel growth curve modeling approach.Results: Individuals who later served in the military had lower rates of depression than their civilian counterparts at year 1 of the study, and rates of depression decreased consistently for both groups throughout the study. Service members ended up with the same level of depression compared to civilians (year 14). Sex, race and parental education were unrelated to depression, and no evidence was found for the hypothesis that the military functions as a "bridging environment" to reduce depression by providing a more attractive alternative compared to civilian life.Conclusions: Individuals who were less depressed at year 1 of the study were more likely to enlist into the military. While both civilians and service members displayed decreasing depression over the years of the study, military members had less decrease in depression over time beginning at a lower level of depression than civilian. Taken together, the minor differences in depression between the civilian and military samples and the lower level of depression among military members at the beginning of the study suggest that military service selects against higher levels of depression at the start of service and, given the known stressors related to the military, membership in the service may be associated with resilience to depression. [ABSTRACT FROM AUTHOR]

Objective: To examine factors affecting children's willingness to share activities with a peer presented as physically handicapped.Method: Participants were 120 elementary school children randomly assigned to view a video of an ambulatory child or the same child in a wheelchair. They rated, on the Shared Activities Questionnaire (SAQ), their own willingness (SAQ-Self) and their perceptions of classmates' willingness (SAQ-Others) to participate in activities with the child.Results: SAQ-Self ratings were consistently higher for the peer in the wheelchair. On the SAQ-Others, differences favoring the child in the wheelchair disappeared, and ratings of this child were lower than SAQ-Self ratings. No interactions were found between ambulation status and age or rater gender or preference for type of shared activity.Conclusions: Children showed highly positive intentions toward a peer in a wheelchair, but intentions attributed to classmates were less positive, which suggests “social desirability” influenced their own ratings. [ABSTRACT FROM AUTHOR]

A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours . The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms. [ABSTRACT FROM PUBLISHER]

The article comments on a decentralized procedure for deciding upon the production and financing of public goods, introduced by T. Groves and J. Ledyard. It was said that the procedure seem to avoid the free rider problem that most economists had believed to be unavoidable when allocating public goods. An example which suggests that there may be difficulties with the proposed mechanism if applied to an economy in which there are many individuals, was presented. The difficulties identified do not concern th existence or optimality of equilibrium. The example suggests that it will be impossible to actually attain an equilibrium under the Groves-Ledyard mechanism if the economy is very large.