55 research outputs found

    Attosecond Precision Multi-km Laser-Microwave Network

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    Synchronous laser-microwave networks delivering attosecond timing precision are highly desirable in many advanced applications, such as geodesy, very-long-baseline interferometry, high-precision navigation and multi-telescope arrays. In particular, rapidly expanding photon science facilities like X-ray free-electron lasers and intense laser beamlines require system-wide attosecond-level synchronization of dozens of optical and microwave signals up to kilometer distances. Once equipped with such precision, these facilities will initiate radically new science by shedding light on molecular and atomic processes happening on the attosecond timescale, such as intramolecular charge transfer, Auger processes and their impact on X-ray imaging. Here, we present for the first time a complete synchronous laser-microwave network with attosecond precision, which is achieved through new metrological devices and careful balancing of fiber nonlinearities and fundamental noise contributions. We demonstrate timing stabilization of a 4.7-km fiber network and remote optical-optical synchronization across a 3.5-km fiber link with an overall timing jitter of 580 and 680 attoseconds RMS, respectively, for over 40 hours. Ultimately we realize a complete laser-microwave network with 950-attosecond timing jitter for 18 hours. This work can enable next-generation attosecond photon-science facilities to revolutionize many research fields from structural biology to material science and chemistry to fundamental physics.Comment: 42 pages, 13 figure

    Sodium Selenide Toxicity Is Mediated by O2-Dependent DNA Breaks

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    Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few experiments studied the direct link between this toxic agent and cell death. To address this question, we first screened a systematic collection of Saccharomyces cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor for hydrogen selenide (H2Se/HSeβˆ’/Se2βˆ’). Among the genes whose deletion caused hypresensitivity, homologous recombination and DNA damage checkpoint genes were over-represented, suggesting that DNA double-strand breaks are a dominant cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly induced DNA phosphodiester-bond breaks via an O2-dependent reaction. The reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl radicals and ruling out participations of superoxide anions or hydrogen peroxide. The β€’OH signature could indeed be detected by electron spin resonance upon exposure of a solution of sodium selenide to O2. Finally we showed that, in vivo, toxicity strictly depended on the presence of O2. Therefore, by combining genome-wide and biochemical approaches, we demonstrated that, in yeast cells, hydrogen selenide induces toxic DNA breaks through an O2-dependent radical-based mechanism

    Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Diabetes mellitus, as well as subsequent ocular complications such as cystoid macular edema (CME), are of fundametal socio-economic relevance. Therefore, we evaluated the influence of internal limiting membrane (ILM) removal on longterm morphological and functional outcome in patients with diabetes mellitus (DM) type 2 and chronic CME without evident vitreomacular traction. METHOD: Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively. Prior focal (n = 31) or panretinal (n = 25) laser coagulation was permitted. Group I (n = 19 patients) underwent surgical induction of posterior vitreous detachment (PVD), group II (n = 20 patients) PVD and removal of the ILM. Eleven patients with detached posterior hyaloid (group III) were not randomized, and ILM removal was performed. One eye had to be excluded from further analysis. Examinations included ETDRS best-corrected visual acuity (BCVA), fluorescein angiography (FLA) and OCT at baseline, 3 and 6 months postoperatively. Main outcome measure was BCVA at 6 months, secondary was foveal thickness. RESULTS: Mean BCVA over 6 months remained unchanged in 85% of patients of group II, and decreased in 53% of patients of group I. Results were not statistically significant different [group I: mean decrease log MAR 95% CI (0.06; 0.32), group II: (-0.02; 0.11)]. OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [group I: mean change: 95% CI (-208.95 ΞΌm; -78.05 ΞΌm), group II: (-80.90 ΞΌm: +59.17 ΞΌm)]. CONCLUSION: Vitrectomy, PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction. ILM delamination shows improved morphological results, and appears to be beneficial in eyes with preexisting PVD

    The transitioning experiences of internationally-educated nurses into a Canadian health care system: A focused ethnography

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    <p>Abstract</p> <p>Background</p> <p>Beyond well-documented credentialing issues, internationally-educated nurses (IENs) may need considerable support in transitioning into new social and health care environments. This study was undertaken to gain an understanding of transitioning experiences of IENs upon relocation to Canada, while creating policy and practice recommendations applicable globally for improving the quality of transitioning and the retention of IENs.</p> <p>Methods</p> <p>A focused ethnography of newly-recruited IENs was conducted, using individual semi-structured interviews at both one-to-three months (Phase 1) and nine-to-twelve months post-relocation (Phase 2). A purposive sample of IENs was recruited during their orientation at a local college, to a health authority within western Canada which had recruited them for employment throughout the region. The interviews were recorded and transcribed, and data was managed using qualitative analytical software. Data analysis was informed by Roper and Shapira's framework for focused ethnography.</p> <p>Results</p> <p>Twenty three IENs consented to participate in 31 interviews. All IENs which indicated interest during their orientation sessions consented to the interviews, yet 14 did not complete the Phase 2 interview due to reorganization of health services and relocation. The ethno-culturally diverse group had an average age of 36.4 years, were primarily educated to first degree level or higher, and were largely (under) employed as "Graduate Nurses". Many IENs reported negative experiences related to their work contract and overall support upon arrival. There were striking differences in nursing practice and some experiences of perceived discrimination. The primary area of discontentment was the apparent communication breakdown at the recruitment stage with subsequent discrepancy in expected professional role and financial reimbursement.</p> <p>Conclusions</p> <p>Explicit and clear communication is needed between employers and recruitment agencies to avoid employment contract misunderstandings and to enable clear interpretation of the credentialing processes. Pre-arrival orientation of IENs including health care communications should be encouraged and supported by the recruiting institution. Moreover, employers should provide more structured and comprehensive workplace orientation to IENs with consistent preceptorship. Similar to findings of many other studies, diversity should be valued and incorporated into the professional culture by nurse managers.</p

    Selenium and Lung Cancer: A Systematic Review and Meta Analysis

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    Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies.Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (β‰₯ 121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61-1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70-3.24); and all-cause-death, OR 0.93 (95%CI 0.79-1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy.Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context

    Evaluating the links between schizophrenia and sleep and circadian rhythm disruption

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    Towards parametric synthesis of millijoule-level two-octave-wide optical waveforms for strong-field experiments

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    We discuss a carrier-envelope phase-stable, 3-channel parametric synthesizer for creating a 2-octave-wide spectrum (0.5-2.2ΞΌ m). The synthesizer output is straightforwardly scalable to the millijoule level with ~1.8-fs pulse duration, rendering it a versatile tool for attosecond science
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