1,2-redox transpositions of tertiary amides

Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule’s reactivity. Herein, we report the 1,2-transposition of the carbon atom oxidation level in cyclic and acyclic tertiary amides, resulting in the one-pot synthesis of 1,2- and 1,3-oxygenated tertiary amines. This oxidation level transfer was facilitated by the careful orchestration of an iridium-catalyzed reduction with the functionalization of transiently formed enamine intermediates. A novel 1,2-carbonyl transposition is described, and the breadth of this redox transposition strategy has been further explored by the development of aminoalcohol and enaminone syntheses. The diverse β-functionalized amine products were shown to be multifaceted and valuable synthetic intermediates, accessing challenging biologically relevant motifs

Enantioselective total synthesis of (+)-incargranine A enabled by bifunctional iminophosphorane and iridium catalysis

Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step

Enantioselective total synthesis of (+)-incargranine A enabled by bifunctional iminophosphorane and iridium catalysis

Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step

Delivering reform in English healthcare: an ideational perspective

A variety of perspectives has been put forward to understand reform across healthcare systems. Recently, some have called for these perspectives to give greater recognition to the role of ideational processes. The purpose of this article is to present an ideational approach to understanding the delivery of healthcare reform. It draws on a case of English healthcare reform – the Next Stage Review led by Lord Darzi – to show how the delivery of its reform proposals was associated with four ideational frames. These frames built on the idea of “progress” in responding to existing problems; the idea of “prevailing policy” in forming part of a bricolage of ideas within institutional contexts; the idea of “prescription” as top-down structural change at odds with local contexts; and the idea of “professional disputes” in challenging the notion of clinical engagement across professional groups. The article discusses the implications of these ideas in furthering our understanding of policy change, conflict and continuity across healthcare settings

Goodpasture's Syndrome: Treatment With Nephrectomy and Renal Transplantation

Three young male patients developed acute glomerulonephritis and serious hemoptysis. All three had evidence of antiglomerular basement membrane (anti-GBM) antibodies in their serum and native kidneys. The pulmonary hemorrhages ceased after bilateral nephrectomy and splenectomy accompanied by irregular treatment with steroids and other immunosuppressants. Renal homotransplantation was successfully carried out from 95 to 162 days later, after circulating anti-GBM antibodies had disappeared. Two of the homografts were biopsied and the third was removed 20, 34, and 2 months posttransplantation, respectively, and contained little or no immunoglobulin. Therefore, Goodpasture's syndrome does not contraindicate renal transplantation under the stipulated conditions of staged therapy. © 1971, American Medical Association. All rights reserved

The last of the simple remainders

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited

Four-lepton production at hadron colliders: aMC@NLO predictions with theoretical uncertainties

We use aMC@NLO to study the production of four charged leptons at the LHC, performing parton showers with both HERWIG and Pythia6. Our underlying matrix element calculation features the full next-to-leading order $O(\alpha_S)$ result and the $O(\alpha_S^2)$ contribution of the $gg$ channel, and it includes all off-shell, spin-correlation, virtual-photon-exchange, and interference effects. We present several key distributions together with the corresponding theoretical uncertainties. These are obtained through a process-independent technique that allows aMC@NLO to compute scale and PDF uncertainties in a fully automated way and at no extra CPU-time costComment: 24 pages, 6 figure

Isotopic liftings of Clifford algebras and applications in elementary particle mass matrices

Isotopic liftings of algebraic structures are investigated in the context of Clifford algebras, where it is defined a new product involving an arbitrary, but fixed, element of the Clifford algebra. This element acts as the unit with respect to the introduced product, and is called isounit. We construct isotopies in both associative and non-associative arbitrary algebras, and examples of these constructions are exhibited using Clifford algebras, which although associative, can generate the octonionic, non-associative, algebra. The whole formalism is developed in a Clifford algebraic arena, giving also the necessary pre-requisites to introduce isotopies of the exterior algebra. The flavor hadronic symmetry of the six u,d,s,c,b,t quarks is shown to be exact, when the generators of the isotopic Lie algebra su(6) are constructed, and the unit of the isotopic Clifford algebra is shown to be a function of the six quark masses. The limits constraining the parameters, that are entries of the representation of the isounit in the isotopic group SU(6), are based on the most recent limits imposed on quark masses.Comment: 19 page

A systematic review of the discriminating biomechanical parameters during the single leg squat

Objective: To determine whether there are common biomechanical parameters when analysing the single leg squat movement to compare pathological and non-pathological groups and whether these parameters are able to effectively distinguish between groups. Methods: Five electronic databases were searched using MESH terms, keywords and phrases across four constructs: squat, biomechanical measures, region of interest, study design. Studies were selected based on inclusion of a quantitative biomechanical measure, compared between a pathological and a non-pathological group, and participants performed a single leg squat movement. Results: Fifteen studies were included and reviewed, where the majority of studies investigated patellofemoral pain. There was considerable variation in the biomechanical outcome measure used to compare between groups. The frontal plane projection angle was the most commonly reported measure. There was considerable variation in the manner in which the single leg squat was performed. Conclusion: Due to variation in how the single leg squat was performed, it was not possible to determine specific biomechanical parameters that distinguish between pathological and non-pathological groups. Frontal plane projection angle appeared to be a parameter that could be effectively utilised. Standardisation of the single leg squat movement is needed to allow comparison between studies of pathological and non-pathological groups

The long-term impact of the MEMA kwa Vijana adolescent sexual and reproductive health intervention: effect of dose and time since intervention exposure.

BACKGROUND: Despite recent decreases in HIV incidence in many sub-Saharan African countries, there is little evidence that specific behavioural interventions have led to a reduction in HIV among young people. Further and wider-scale decreases in HIV require better understanding of when behaviour change occurs and why. The MEMA kwa Vijana adolescent sexual and reproductive health intervention has been implemented in rural Mwanza, Tanzania since 1999. A long-term evaluation in 2007/8 found that the intervention improved knowledge, attitudes to sex and some reported risk behaviours, but not HIV or HSV2 prevalence. The aim of this paper was to assess the differential impact of the intervention according to gender, age, marital status, number of years of exposure and time since last exposure to the intervention. METHODS: In 2007, a cross-sectional survey was conducted in the 20 trial communities among 13,814 young people (15-30 yrs) who had attended intervention or comparison schools between 1999 and 2002. Outcomes for which the intervention had an impact in 2001 or 2007 were included in this subgroup analysis. Data were analysed using cluster-level methods for stratified cluster-randomised trials, using interaction tests to determine if intervention impact differed by subgroup. RESULTS: Taking into account multiplicity of testing, concurrence with a priori hypotheses and consistency within the results no strong effect-modifiers emerged. Impact on pregnancy knowledge and reported attitudes to sex increased with years of exposure to high-quality intervention. CONCLUSIONS: The desirable long-term impact of the MEMA kwa Vijana intervention did not vary greatly according to the subgroups examined. This suggests that the intervention can have an impact on a broad cross-section of young people in rural Mwanza. TRIAL REGISTRATION: ClinicalTrials.gov NCT00248469