Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection

BACKGROUND: The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S(4) is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S(4) belongs to the most virulent subspecies of F. tularensis, subspecies tularensis. METHODS: In this study, we investigated the relative virulence of Schu S(4) in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S(4) at drop point. RESULTS: Survival curve comparisons demonstrate that the Schu S(4) strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S(4) or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987. CONCLUSIONS: The knowledge gained from using Schu S(4) as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results

Exposure to Household Air Pollution from Biomass-Burning Cookstoves and HbA1c and Diabetic Status Among Honduran Women

Household air pollution from biomass cookstoves is estimated to be responsible for more than two and a half million premature deaths annually, primarily in low and middle‐income countries where cardiometabolic disorders, such as Type II Diabetes, are increasing. Growing evidence supports a link between ambient air pollution and diabetes, but evidence for household air pollution is limited. This cross‐sectional study of 142 women (72 with traditional stoves and 70 with cleaner‐burning Justa stoves) in rural Honduras evaluated the association of exposure to household air pollution (stove type, 24‐hour average kitchen and personal fine particulate matter [PM2.5] mass and black carbon) with glycated hemoglobin (HbA1c) levels and diabetic status based on HbA1c levels. The prevalence ratio (PR) per interquartile range increase in pollution concentration indicated higher prevalence of prediabetes/diabetes (vs normal HbA1c) for all pollutant measures (eg, PR per 84 μg/m3 increase in personal PM2.5, 1.49; 95% confidence interval [CI], 1.11‐2.01). Results for HbA1c as a continuous variable were generally in the hypothesized direction. These results provide some evidence linking household air pollution with the prevalence of prediabetes/diabetes, and, if confirmed, suggest that the global public health impact of household air pollution may be broader than currently estimated

Formation and Evolution of the Disk System of the Milky Way: [alpha/Fe] Ratios and Kinematics of the SEGUE G-Dwarf Sample

We employ measurements of the [alpha/Fe] ratio derived from low-resolution (R~2000) spectra of 17,277 G-type dwarfs from the SEGUE survey to separate them into likely thin- and thick-disk subsamples. Both subsamples exhibit strong gradients of orbital rotational velocity with metallicity, of opposite signs, -20 to -30 km/s/dex for the thin-disk and +40 to +50 km/s/dex for the thick-disk population. The rotational velocity is uncorrelated with Galactocentric distance for the thin-disk subsample, and exhibits a small trend for the thick-disk subsample. The rotational velocity decreases with distance from the plane for both disk components, with similar slopes (-9.0 {\pm} 1.0 km/s/kpc). Thick-disk stars exhibit a strong trend of orbital eccentricity with metallicity (about -0.2/dex), while the eccentricity does not change with metallicity for the thin-disk subsample. The eccentricity is almost independent of Galactocentric radius for the thin-disk population, while a marginal gradient of the eccentricity with radius exists for the thick-disk population. Both subsamples possess similar positive gradients of eccentricity with distance from the Galactic plane. The shapes of the eccentricity distributions for the thin- and thick-disk populations are independent of distance from the plane, and include no significant numbers of stars with eccentricity above 0.6. Among several contemporary models of disk evolution we consider, radial migration appears to have played an important role in the evolution of the thin-disk population, but possibly less so for the thick disk, relative to the gas-rich merger or disk heating scenarios. We emphasize that more physically realistic models and simulations need to be constructed in order to carry out the detailed quantitative comparisons that our new data enable.Comment: Accepted for publication in ApJ, 18 pages, 12 figures, 2 tables, emulateapj forma

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

Combined histomorphometric and gene-expression profiling applied to toxicology

We have developed a unique methodology for the combined analysis of histomorphometric and gene-expression profiles amenable to intensive data mining and multisample comparison for a comprehensive approach to toxicology. This hybrid technology, termed extensible morphometric relational gene-expression analysis (EMeRGE), is applied in a toxicological study of time-varied vehicle- and carbon-tetrachloride (CCl(4))-treated rats, and demonstrates correlations between specific genes and tissue structures that can augment interpretation of biological observations and diagnosis

Star formation in bulgeless late type galaxies: clues to their evolution

We present GMRT 1280 MHz radio continuum observations and follow-up optical studies of the disk and nuclear star formation in a sample of low luminosity bulgeless galaxies. The main aim is to understand bulge formation and overall disk evolution in these late type galaxies. We detected radio continuum from five of the twelve galaxies in our sample; the emission is mainly associated with disk star formation. Only two of the detected galaxies had extended radio emission; the others had patchy disk emission. In the former two galaxies, NGC3445 and NGC4027, the radio continuum is associated with star formation triggered by tidal interactions with nearby companion galaxies. We did follow-up Halpha imaging and nuclear spectroscopy of both galaxies using the Himalayan Chandra Telescope (HCT). The Halpha emission is mainly associated with the strong spiral arms. The nuclear spectra indicate ongoing nuclear star formation in NGC3445 and NGC4027 which maybe associated with nuclear star clusters. No obvious signs of AGN activity were detected. Although nearly bulgeless, both galaxies appear to have central oval distortions in the R band images; these could represent pseudobulges that may later evolve into large bulges. We thus conclude that tidal interactions are an important means of bulge formation and disk evolution in bulgeless galaxies; without such triggers these galaxies appear to be low in star formation and overall disk evolution.Comment: 12 pages, 14 figures, to appear in MNRA

Exposure to household air pollution from biomassâ burning cookstoves and HbA1c and diabetic status among Honduran women

Household air pollution from biomass cookstoves is estimated to be responsible for more than two and a half million premature deaths annually, primarily in low and middleâ income countries where cardiometabolic disorders, such as Type II Diabetes, are increasing. Growing evidence supports a link between ambient air pollution and diabetes, but evidence for household air pollution is limited. This crossâ sectional study of 142 women (72 with traditional stoves and 70 with cleanerâ burning Justa stoves) in rural Honduras evaluated the association of exposure to household air pollution (stove type, 24â hour average kitchen and personal fine particulate matter [PM2.5] mass and black carbon) with glycated hemoglobin (HbA1c) levels and diabetic status based on HbA1c levels. The prevalence ratio (PR) per interquartile range increase in pollution concentration indicated higher prevalence of prediabetes/diabetes (vs normal HbA1c) for all pollutant measures (eg, PR per 84 μg/m3 increase in personal PM2.5, 1.49; 95% confidence interval [CI], 1.11â 2.01). Results for HbA1c as a continuous variable were generally in the hypothesized direction. These results provide some evidence linking household air pollution with the prevalence of prediabetes/diabetes, and, if confirmed, suggest that the global public health impact of household air pollution may be broader than currently estimated.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145588/1/ina12484_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145588/2/ina12484.pd

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Two Stellar Components in the Halo of the Milky Way

The halo of the Milky Way provides unique elemental abundance and kinematic information on the first objects to form in the Universe, which can be used to tightly constrain models of galaxy formation and evolution. Although the halo was once considered a single component, evidence for its dichotomy has slowly emerged in recent years from inspection of small samples of halo objects. Here we show that the halo is indeed clearly divisible into two broadly overlapping structural components -- an inner and an outer halo -- that exhibit different spatial density profiles, stellar orbits and stellar metallicities (abundances of elements heavier than helium). The inner halo has a modest net prograde rotation, whereas the outer halo exhibits a net retrograde rotation and a peak metallicity one-third that of the inner halo. These properties indicate that the individual halo components probably formed in fundamentally different ways, through successive dissipational (inner) and dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.Comment: Two stand-alone files in manuscript, concatenated together. The first is for the main paper, the second for supplementary information. The version is consistent with the version published in Natur