Gold(I)-Catalysed Direct Thioetherifications Using Allylic Alcohols: an Experimental and Computational Study

A gold(I)-catalysed direct thioetherification reaction between allylic alcohols and thiols is presented. The reaction is generally highly regioselective (S(N)2′). This dehydrative allylation procedure is very mild and atom economical, producing only water as the by-product and avoiding any unnecessary waste/steps associated with installing a leaving or activating group on the substrate. Computational studies are presented to gain insight into the mechanism of the reaction. Calculations indicate that the regioselectivity is under equilibrium control and is ultimately dictated by the thermodynamic stability of the products

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment

Treatment for CIN is usually undertaken in an outpatient colposcopy clinic to remove the pre-cancerous cells from the cervix. It commonly involves lifting the cells off the cervix with electrically heated wire (diathermy) or laser, or destroying the abnormal cells with freezing methods (cryotherapy). This is potentially a painful procedure. The purpose of this review is to determine which, if any, pain relief should be used during cervical colposcopy treatment. We identified 17 trials and these reported different forms of pain relief before, during and after colposcopy. Evidence from two small trials showed that women having a colposcopy treatment had less pain and blood loss if the cervix was injected with a combination of a local anaesthetic drug and a drug that causes blood vessels to constrict (narrow), compared with placebo. Although taking oral pain-relieving drugs (e.g. ibuprofen) before treatment on the cervix in the colposcopy clinic is recommended by most guidelines, evidence from two small trials did not show that this practice reduced pain during the procedure. Most of the evidence in this field is of a low to moderate quality and further research may change these findings. Additionally, we were unable to obtain evidence with regards to dosage of the local anaesthetic drug or method of administering local anaesthetic into the cervix. There is need for high-quality trials with sufficient numbers of participants in order to provide the data necessary to estimate these effects

Imaging Extended Emission-Line Regions of Obscured AGN with the Subaru Hyper Suprime-Cam Survey

Narrow-line regions excited by active galactic nuclei (AGN) are important for studying AGN photoionization and feedback. Their strong [O III] lines can be detected with broadband images, allowing morphological studies of these systems with large-area imaging surveys. We develop a new technique to reconstruct the [O III] images using the Subaru Hyper Suprime-Cam (HSC) Survey aided with spectra from the Sloan Digital Sky Survey (SDSS). The technique involves a careful subtraction of the galactic continuum to isolate emission from the [O III]$\lambda$5007 and [O III]$\lambda$4959 lines. Compared to traditional targeted observations, this technique is more efficient at covering larger samples with less dedicated observational resources. We apply this technique to an SDSS spectroscopically selected sample of 300 obscured AGN at redshifts 0.1 - 0.7, uncovering extended emission-line region candidates with sizes up to tens of kpc. With the largest sample of uniformly derived narrow-line region sizes, we revisit the narrow-line region size-luminosity relation. The area and radii of the [O III] emission-line regions are strongly correlated with the AGN luminosity inferred from the mid-infrared (15 $\mu$m rest-frame) with a power-law slope of $0.62^{+0.05}_{-0.06} \pm 0.10$ (statistical and systemic errors), consistent with previous spectroscopic findings. We discuss the implications for the physics of AGN emission-line region and future applications of this technique, which should be useful for current and next-generation imaging surveys to study AGN photoionization and feedback with large statistical samples.Comment: 20 pages, 13 figures, MNRAS submitte

Extremely long quasiparticle spin lifetimes in superconducting aluminium using MgO tunnel spin injectors

There has been an intense search in recent years for long-lived spin-polarized carriers for spintronic and quantum-computing devices. Here we report that spin polarized quasi-particles in superconducting aluminum layers have surprisingly long spin-lifetimes, nearly a million times longer than in their normal state. The lifetime is determined from the suppression of the aluminum's superconductivity resulting from the accumulation of spin polarized carriers in the aluminum layer using tunnel spin injectors. A Hanle effect, observed in the presence of small in-plane orthogonal fields, is shown to be quantitatively consistent with the presence of long-lived spin polarized quasi-particles. Our experiments show that the superconducting state can be significantly modified by small electric currents, much smaller than the critical current, which is potentially useful for devices involving superconducting qubits

Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)

Introducing EMMIE: An evidence rating scale to encourage mixed-method crime prevention synthesis reviews

Objectives This short report describes the need for, and the development of, a coding system to distil the quality and coverage of systematic reviews of the evidence relating to crime prevention interventions. The starting point for the coding system concerns the evidence needs of policymakers and practitioners. Methods The coding scheme (EMMIE) proposed builds on previous scales that have been developed to assess the probity, coverage and utility of evidence both in health and criminal justice. It also draws on the principles of realist synthesis and review. Results The proposed EMMIE scale identifies five dimensions to which systematic reviews intended to inform crime prevention should speak. These are the Effect of intervention, the identification of the causal Mechanism(s) through which interventions are intended to work, the factors that Moderate their impact, the articulation of practical Implementation issues, and the Economic costs of intervention

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

Delocalized single-photon Dicke states and the Leggett- Garg inequality in solid state systems

We show how to realize a single-photon Dicke state in a large one-dimensional array of two- level systems, and discuss how to test its quantum properties. Realization of single-photon Dicke states relies on the cooperative nature of the interaction between a field reservoir and an array of two-level-emitters. The resulting dynamics of the delocalized state can display Rabi-like oscillations when the number of two-level emitters exceeds several hundred. In this case the large array of emitters is essentially behaving like a mirror-less cavity. We outline how this might be realized using a multiple-quantum-well structure and discuss how the quantum nature of these oscillations could be tested with the Leggett-Garg inequality and its extensions.Comment: 29 pages, 5 figures, journal pape

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR