Hyperoxia Depletes (6R)-5,6,7,8-Tetrahydrobiopterin Levels in the Neonatal Retina: Implications for Nitric Oxide Synthase Function in Retinopathy

Retinopathy of prematurity is a sight-threatening complication of premature birth caused by nitrooxidativeinsult to the developing retinal vasculature during therapeutic hyperoxia exposure and laterischemia-induced neovascularization on supplemental oxygen withdrawal. In the vasodegenerativephase, during hyperoxia, defective endothelial nitric oxide synthase (NOS) produces reactive oxygenand nitrogen free radicals rather than vasoprotective nitric oxide for unclear reasons. More important,NOS critically depends on the availability of the cofactor (6R)-5,6,7,8-tetrahydrobiopterin (BH4).Because BH4 synthesis is controlled enzymatically by GTP cyclohydrolase (GTPCH), we used GTPCHdepletedmice [hyperphenylalanaemia strain Q4 (hph1)] to investigate the impact of hyperoxia on BH4bioavailability and retinal vascular pathology in the neonate. Hyperoxia decreased BH4 in retinas,lungs, and aortas in all experimental groups, resulting in a dose-dependent decrease in NOS activityand, in the wild-type group, elevated NOS-derived superoxide. Retinal dopamine levels were similarlydiminished, consistent with the dependence of tyrosine hydroxylase on BH4. Despite greater depletionof BH4, the hphþ/ and hph1/ groups did not show exacerbated hyperoxia-induced vessel closure,but exhibited greater vascular protection and reduced progression to neovascular disease. This vasoprotectiveeffect was independent of enhanced circulating vascular endothelial growth factor (VEGF),which was reduced by hyperoxia, but Q5 to local ganglion cell layerederived VEGF. A constitutively higherlevel of VEGF expression associated with retinal development protects GTPCH-deficient neonates fromoxygen-induced vascular damage.

Energy levels, radiative rates and lifetimes for transitions in Br-like ions with 38 ≤ Z ≤ 42

Energy levels and radiative rates for transitions in five Br-like ions (Sr IV, Y V, Zr VI, Nb VII and Mo VIII) are calculated with the general-purpose relativistic atomic structure package (GRASP). Extensive configuration interaction has been included and results are presented among the lowest 31 levels of the 4s²4p⁵, 4s²4p⁴4d and 4s4p⁶ configurations. Lifetimes for these levels have also been determined, although unfortunately no measurements are available with which to compare. However, recently theoretical results have been reported by Singh et al (2013 Phys. Scr. 88 035301) using the same GRASP code. But their reported data for radiative rates and lifetimes cannot be reproduced and show discrepancies of up to five orders of magnitude with the present calculations.

Energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 21≤Z≤28

We report calculations of energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 21≤Z≤28. The General-Purpose Relativistic Atomic Structure Package is adopted for calculating energy levels and radiative rates, while for determining the collision strengths and subsequently the excitation rates, the Dirac Atomic R-matrix Code is used. Oscillator strengths, radiative rates, and line strengths are listed for all E1, E2, M1, and M2 transitions among the lowest 24 levels of the Li-like ions considered. Collision strengths have been averaged over a Maxwellian velocity distribution, and the effective collision strengths obtained are given over a wide temperature range up to 10^7.8 K. Additionally, lifetimes are listed for all calculated levels of these ions. Finally, extensive comparisons are made with results available in the literature, as well as with our analogous calculations for all parameters with the Flexible Atomic Code, in order to assess the accuracy of the results.

Energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 12≤Z≤20

We report calculations of energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 12≤Z≤20. The grasp (general-purpose relativistic atomic structure package) is adopted for calculating energy levels and radiative rates, while for determining the collision strengths and subsequently the excitation rates, the Dirac atomic R-matrix code is used. Oscillator strengths, radiative rates, and line strengths are reported for all E1, E2, M1, and M2 transitions among the lowest 24 levels of the Li-like ions considered. Collision strengths have been averaged over a Maxwellian velocity distribution, and the effective collision strengths obtained are reported over a wide temperature range up to 10^7.4 K. Additionally, lifetimes are also listed for all calculated levels of the ions. Finally, extensive comparisons are made with results available in the literature, as well as with our parallel calculations for all parameters with the Flexible Atomic Code, in order to assess the accuracy of the reported results. 

Phenotypic characterization of an international Pseudomonas aeruginosa reference panel: strains of cystic fibrosis (CF) origin show less in vivo virulence than non-CF strains

Pseudomonas aeruginosa causes chronic lung infections in people with cystic fibrosis (CF) and acute opportunistic infections in people without CF. Forty two P. aeruginosa strains from a range of clinical and environmental sources were collated into a single reference strain panel to harmonise research on this diverse opportunistic pathogen. To facilitate further harmonized and comparable research on P. aeruginosa, we characterised the panel strains for growth rates, motility, virulence in the Galleria mellonella infection model, pyocyanin and alginate production, mucoid phenotype, lipopolysaccharide (LPS) pattern, biofilm formation, urease activity, antimicrobial and phage susceptibilities. Phenotypic diversity across the P. aeruginosa panel was apparent for all phenotypes examined agreeing with the marked variability seen in this species. However, except for growth rate, the phenotypic diversity among strains from CF versus non-CF sources was comparable. CF strains were less virulent in the G. mellonella model than non-CF strains (p=0.037). Transmissible CF strains generally lacked O antigen, produced less pyocyanin, and had low virulence in G. mellonella. Further, in the three sets of sequential CF strains, virulence, O-antigen expression and pyocyanin production were higher in the earlier isolate compared to the isolate obtained later in infection. Overall, full phenotypic characterization of the defined panel of P. aeruginosa strains increases our understanding of the virulence and pathogenesis of P. aeruginosa and may provide a valuable resource for the testing of novel therapies against this problematic pathogen.

PS1-10afx at z = 1.388: Pan-STARRS1 Discovery of a New Type of Superluminous Supernova

We present the Pan-STARRS1 discovery of PS1-10afx, a unique hydrogen-deficient superluminous supernova (SLSN) at redshift z = 1.388. The light curve peaked at z P1 = 21.7 mag, making PS1-10afx comparable to the most luminous known SNe, with Mu = -22.3 mag. Our extensive optical and near-infrared observations indicate that the bolometric light curve of PS1-10afx rose on the unusually fast timescale of ~12 days to the extraordinary peak luminosity of 4.1 × 1044 erg s-1 (M bol = -22.8 mag) and subsequently faded rapidly. Equally important, the spectral energy distribution is unusually red for an SLSN, with a color temperature of ~6800 K near maximum light, in contrast to previous hydrogen-poor SLSNe, which are bright in the ultraviolet (UV). The spectra more closely resemble those of a normal SN Ic than any known SLSN, with a photospheric velocity of ~11, 000 km s-1 and evidence for line blanketing in the rest-frame UV. Despite the fast rise, these parameters imply a very large emitting radius (gsim 5 × 1015 cm). We demonstrate that no existing theoretical model can satisfactorily explain this combination of properties: (1) a nickel-powered light curve cannot match the combination of high peak luminosity with the fast timescale; (2) models powered by the spindown energy of a rapidly rotating magnetar predict significantly hotter and faster ejecta; and (3) models invoking shock breakout through a dense circumstellar medium cannot explain the observed spectra or color evolution. The host galaxy is well detected in pre-explosion imaging with a luminosity near L*, a star formation rate of ~15 M ⊙ yr-1, and is fairly massive (~2 × 1010 M ⊙), with a stellar population age of ~108 yr, also in contrast to the young dwarf hosts of known hydrogen-poor SLSNe. PS1-10afx is distinct from known examples of SLSNe in its spectra, colors, light-curve shape, and host galaxy properties, suggesting that it resulted from a different channel than other hydrogen-poor SLSNe.

Potentially inappropriate prescribing in two populations with differing socio-economic profiles: a cross-sectional database study using the PROMPT criteria

PURPOSE: The purpose of this study is to establish the prevalence of potentially inappropriate prescribing (PIP) in middle-aged adults (45-64 years) in two populations with differing socio-economic profiles, and to investigate factors associated with PIP, using the PROMPT (PRescribing Optimally in Middle-aged People's Treatments) criteria.METHODS: A retrospective cross-sectional study was conducted using 2012 data from the Enhanced Prescribing Database (EPD), covering the full population in Northern Ireland and the Health Services Executive Primary Care Reimbursement Service (HSE-PCRS) database, covering the most socio-economically deprived third of the population in this age group in the Republic of Ireland. The prevalence for each PROMPT criterion and overall prevalence of PIP were calculated. Logistic regression was used to investigate the association between PIP and gender, age group and polypharmacy.RESULTS: This study included 441,925 patients from the EPD and 309,748 patients from the HSE-PCRS database. Polypharmacy was common in both datasets (46.7 % in the HSE-PCRS and 20.3 % in the EPD). The prevalence of PIP was 42.9 % (95%CI 42.7, 43.1) in the HSE-PCRS and 21.1 % (95%CI 21.0, 21.2) in the EPD. Age group, female gender and polypharmacy were significantly associated with PIP in both populations (p < 0.05) and polypharmacy had the strongest association.CONCLUSIONS: PIP is common amongst middle-aged people with the risk of PIP increasing with polypharmacy. Differences in the prevalence of polypharmacy and PIP between the two populations may relate to heterogeneity in healthcare services and different socio-economic profiles, with higher rates of multimorbidity and associated polypharmacy in more deprived groups.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.