The association between pre-hospital antibiotic therapy and subsequent in-hospital mortality in adults presenting with community-acquired pneumonia: an observational study.

BACKGROUND: The majority of patients with community acquired-pneumonia (CAP) are treated in primary care and the mortality in this group is very low. However, a small but significant proportion of patients who begin treatment in the community subsequently require admission due to symptomatic deterioration. This study compared patients who received community antibiotics prior to admission to those who had not, and looked for associations with clinical outcomes. METHODS: This study analysed the Advancing Quality (AQ) Pneumonia database of patients admitted with CAP to 9 acute hospitals in the northwest of England over a 12-month period. RESULTS: There were 6348 subjects (mean age 72 [SD 16] years; gender ratio 1:1) admitted with CAP, of whom 17% had been pre-treated with antibiotics. The in-hospital mortality was 18.6% for the pre-treatment group compared to 13.2% in the "antibiotic naïve" group (p < 0.001). On multivariate analysis, age, male gender and antibiotic pre-treatment were predictors of in-hospital mortality along with a history of cerebrovascular accident, congestive cardiac failure, dementia, renal disease and cancer. After adjustment for CURB-65 score, age, co-morbidities and pre-treatment with antibiotics remained as independent risk factors for in-hospital mortality (OR 1.43, 95% CI 1.19-1.71). CONCLUSION: CAP patients admitted to hospital were more likely to die during admission if they had received antibiotics for the same illness pre-admission. Future studies should endeavor to determine the mechanisms underlying this association, such as microbiological factors and the role of comorbidities. Patients hospitalized with CAP despite prior antibiotic treatment in the community require close monitoring.

Aliovalent Cation Substitution in UO2: Electronic and Local Structures of U1-yLayO2±x Solid Solutions.

For nuclear fuel related applications, the oxygen stoichiometry of mixed oxides U1-yMyO2±x is an essential property as it affects fuel properties and may endanger the safe operation of nuclear reactors. A careful review of the open literature indicates that this parameter is difficult to assess properly and that the nature of the defects, i.e., oxygen vacancies or UV, in aliovalent cation-doped UO2 is still subject to controversy. To confirm the formation of UV, we have investigated the room-temperature stable U1-yLayO2±x phase using several experimental methods (e.g., XRD, XANES, and NMR) confirmed by theoretical calculations. This paper presents the experimental proof of UV and its effect we identified in both electronic and local structure. We observe that UV is formed in quasi-equimolar proportion as LaIII in U1-yLayO2±x (y = 0.06, 0.11, and 0.22) solid solutions. The fluorite structure is maintained despite the cationic substitution, but the local structure is affected as variations of the interatomic distances are found. Therefore, we provide here the definitive proof that the substitution of UIV with LaIII is not accommodated by the creation of O vacancies as has often been assumed. The UO2 fluorite structure compensates the incorporation of an aliovalent cation by the formation of UV in quasi-equimolar proportions.

Fingerprint of local disorder in long range ordered isometric pyrochlores.

The detailed characterization of local order and disorder in isometric A2B2O7 crystalline pyrochlores is of significant importance in view of their wide range and sensitive technological applications. Nevertheless, much remains to be understood concerning their atomic scale structures. Here we specifically pinpoint local order and disorder in four stoichiometric Ln2Zr2O7 (Ln = La, Nd, Sm and Eu) pyrochlores using a combination of three standard easily available laboratory techniques: XRD, 17O solid-state MAS NMR and Raman spectroscopy. The evolution of the oxygen sub-lattice identifies specific features (extra 17O NMR signals and Raman bands) which undoubtedly reveal local oxygen order and disorder in these stoichiometric long range ordered crystalline pyrochlores. These results complete the understanding of the atomic scale in these stoichiometric pyrochlores necessitating the need for new microscopic structural models.

Self-healing capacity of nuclear glass observed by NMR spectroscopy.

Safe management of high level nuclear waste is a worldwide significant issue for which vitrification has been selected by many countries. There exists a crucial need for improving our understanding of the ageing of the glass under irradiation. While external irradiation by ions provides a rapid simulation of damage induced by alpha decays, short lived actinide doping is more representative of the reality. Here, we report radiological NMR experiments to compare the damage in International Simplified Glass (ISG) when irradiated by these two methods. In the 0.1 mole percent (244)Cm doped glass, accumulation of high alpha decay only shows small modifications of the local structure, in sharp contrast to heavy ion irradiation. These results reveal the ability of the alpha particle to partially repair the damage generated by the heavy recoil nuclei highlighting the radiation resistance of nuclear glass and the difficulty to accurately simulate its behaviour by single ion beam irradiations.

Further insights into the chemistry of the Bi-U-O system.

Cubic fluorite-type phases have been reported in the U(IV)O2-Bi2O3 system for the entire compositional range, but an unusual non-linear variation of the lattice parameter with uranium substitution has been observed. In the current extensive investigation of the uranium(iv) oxide-bismuth(iii) oxide system, this behaviour of the lattice parameter evolution with composition has been confirmed and its origin identified. Even under inert atmosphere at 800 °C, U(IV) oxidises to U(V)/U(VI) as a function of the substitution degree. Thus, using a combination of three methods (XRD, XANES and Raman) we have identified the formation of the BiU(V)O4 and Bi2U(VI)O6 compounds, within this series. Moreover, we present here the Rietveld refinement of BiU(V)O4 at room temperature and we report the thermal expansion of both BiU(V)O4 and Bi2U(VI)O6 compounds.

Structural Investigation of (U0.7Pu0.3)O2-x Mixed Oxides.

Uranium-plutonium mixed oxide containing 30% of plutonium is a candidate fuel for several fast neutron and accelerator driven reactor systems. In this work, a detailed structural investigation on sol-gel synthesized stoichiometric U0.7Pu0.3O2.00 and substoichiometric U0.7Pu0.3O2-x, using X-ray diffraction (XRD), oxygen 17 magic angle spinning nuclear magnetic resonance ((17)O MAS NMR) and X-ray absorption spectroscopy is described. As observed by XRD, the stoichiometric U0.7Pu0.3O2.00 is monophasic with a lattice parameter in good agreement with Vegard's law, while the substoichiometric U0.7Pu0.3O2-x material is biphasic. Solid solution ideality in terms of a random distribution of metal atoms is proven for U0.7Pu0.3O2.00 with (17)O MAS NMR. X-ray absorption near-edge structure (XANES) spectroscopy shows the presence of plutonium(III) in U0.7Pu0.3O2-x. Extended X-ray absorption fine-structure (EXAFS) spectroscopy indicates a similar local structure around both cations, and comparison with XRD indicates a close similarity between uranium and plutonium local structures and the long-range ordering.

High-resolution solid-state oxygen-17 NMR of actinide-bearing compounds: an insight into the 5f chemistry.

A massive interest has been generated lately by the improvement of solid-state magic-angle spinning (MAS) NMR methods for the study of a broad range of paramagnetic organic and inorganic materials. The open-shell cations at the origin of this paramagnetism can be metals, transition metals, or rare-earth elements. Actinide-bearing compounds and their 5f unpaired electrons remain elusive in this intensive research area due to their well-known high radiotoxicity. A dedicated effort enabling the handling of these highly radioactive materials now allows their analysis using high-resolution MAS NMR (>55 kHz). Here, the study of the local structure of a series of actinide dioxides, namely, ThO2, UO2, NpO2, PuO2, and AmO2, using solid-state (17)O MAS NMR is reported. An important increase of the spectral resolution is found due to the removal of the dipolar broadening proving the efficiency of this technique for structural analysis. The NMR parameters in these systems with numerous and unpaired 5f electrons were interpreted using an empirical approach. Single-ion model calculations were performed for the first time to determine the z component of electron spin on each of the actinide atoms, which is proportional to the shifts. A similar variation thereof was observed only for the heavier actinides of this study.

Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13.

The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would therefore be a novel disease modifying therapy for the treatment of arthritis. Our efforts have resulted in the discovery of a series of carboxylic acid inhibitors of MMP-13 that do not significantly inhibit the related MMP-1 (collagenase-1) or tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE). It has previously been suggested (but not proven) that inhibition of the latter two enzymes could lead to side effects. A promising carboxylic acid lead 9 was identified and a convergent synthesis developed. This paper describes the optimization of 9 and the identification of a compound 24f for further development. Compound 24f is a subnanomolar inhibitor of MMP-13 (IC(50) value 0.5 nM and K(i) of 0.19 nM) having no activity against MMP-1 or TACE (IC(50) of >10000 nM). Furthermore, in a rat model of MMP-13-induced cartilage degradation, 24f significantly reduced proteoglycan release following oral dosing at 30 mg/kg (75% inhibition, p < 0.05) and at 10 mg/kg (40% inhibition, p < 0.05).

Exposures to diesel exhaust in the International Brotherhood of Teamsters, 1950-1990.

A prior case-control study found a positive, monotonic exposure-response relationship between exposure to diesel exhaust and lung cancer among decedents of the Central States Conference of the International Brotherhood of Teamsters. In response to critiques of the Teamsters' exposure estimates by the Health Effects Institute's Diesel Epidemiology Panel, historical exposures and associated uncertainties are investigated here. Historic diesel exhaust exposures are predicted as a function of heavy-duty diesel truck emissions, increasing use of diesel engines, and occupational elemental carbon (EC) measurements taken during the late 1980s and early 1990s. EC from diesel and nondiesel sources is distinguished in light of recent studies indicating a substantial contribution of gasoline vehicles to ambient EC. Monte Carlo sampling is used to characterize exposure distributions. The methodology used in this article-a probabilistic model for historical exposure assessment-is novel.

National vehicle emissions policies and practices and declining US carbon monoxide-related mortality.

CONTEXT: Carbon monoxide (CO) has been reported to contribute to more than 2000 poisoning deaths per year in the United States. OBJECTIVES: To evaluate the influence of national vehicle emissions policies and practices on CO-related mortality and to describe 31 years (1968-1998) of CO-related deaths in the United States. DESIGN AND SETTING: Longitudinal trend analysis using computerized death data from the Centers for Disease Control and Prevention, US Census Bureau population data, and annual CO emissions estimates for light-duty vehicles provided by the US Environmental Protection Agency. MAIN OUTCOME MEASURE: All deaths in the US for which non-fire-related CO poisoning was an underlying or contributing condition, classified by intent and mechanism of death. Negative binomial regression was used to incorporate every year of data into estimated percentage changes in CO emissions and mortality rates over time. RESULTS: During 1968-1998, CO-related mortality rates in the United States declined from 20.2 deaths to 8.8 deaths per 1 million person-years (an estimated decline of 57.8%; 95% confidence interval [CI], -62.4% to -52.6%). Following the introduction of the catalytic converter to automobiles in 1975, CO emissions from automobiles decreased by an estimated 76.3% of 1975 levels (95% CI, -82.0% to -70.4%) and unintentional motor vehicle-related CO death rates declined from 4.0 to 0.9 deaths per 1 million person-years (an estimated decline of 81.3%; 95% CI, -84.8% to -77.0%). Rates of motor vehicle-related CO suicides declined from 10.0 to 4.9 deaths per 1 million person-years (an estimated decline of 43.3%; 95% CI, -57.5% to -24.3%). During 1975-1996, an annual decrease of 10 g/mile of estimated CO emissions from automobiles was associated with a 21.3% decrease (95% CI, -24.2% to -18.4%) in the annual unintentional motor vehicle-related CO death rate and a 5.9% decrease (95%CI, -10.0% to -1.8%) in the annual rate of motor vehicle-related CO suicides. CONCLUSIONS: If rates of unintentional CO-related deaths had remained at pre-1975 levels, an estimated additional 11 700 motor vehicle-related CO poisoning deaths might have occurred by 1998. This decline in death rates appears to be a public health benefit associated with the enforcement of standards set by the 1970 Clean Air Act.