Stereocontrolled Semisyntheses of Elliptone and 12aβ-Hydroxyelliptone.

Operationally simple, stereocontrolled semisyntheses of the anticancer rotenoids elliptone and 12aβ-hydroxyelliptone, isolated from Derris elliptica and Derris trifoliata, respectively, are described. Inspired by the work of Singhal, elliptone was prepared from rotenone via a dihydroxylation-oxidative cleavage, chemoselective Baeyer-Villiger oxidation, and acid-catalyzed elimination sequence. Elaboration of elliptone to 12aβ-hydroxyelliptone was achieved via a diastereoselective chromium-mediated Étard-like hydroxylation. The semisynthesis of elliptone constitutes an improvement over previous methods in terms of safety, scalability, and yield, while the first synthesis of 12aβ-hydroxyelliptone is also described.This research was supported by the EPSRC, BBSRC, MRC, Wellcome Trust, and ERC (FP7/2007-2013; 279337/DOS). D.A.R. thanks Cancer Research UK for funding. W.J.S.F. thanks A*STAR Singapore for funding. D.G.T. thanks AstraZeneca for funding. D.R.S. acknowledges support from a Royal Society Wolfson Research Merit award

Bioinspired Total Synthesis of Bussealin E.

The first total synthesis of bussealin E, a natural product with a unique cycloheptadibenzofuran scaffold, is reported. A strategy inspired by a proposed biosynthesis was employed whereby a diphenylpropane derivative underwent an oxidative phenolic coupling to forge the tetracyclic ring system. The synthesis of the diphenylpropane featured a key sp2-sp3 Hiyama coupling between a vinyldisiloxane and a benzylic bromide

Stepping up to a new level: effects of blurring vision

PURPOSE. To determine the effects of blurring vision on wholebody center-of-mass (CM) dynamics and foot-clearance parameters in elderly individuals performing a single step up to a new level. METHODS. Twelve healthy subjects (mean age, 72.3 Ϯ4.17 years) performed a single step up to a new level (heights of 73 and 146 mm). Trials were undertaken with vision optimally corrected and with vision diffusively blurred by light-scattering lenses (cataract simulation). CM and foot-clearance parameter data were assessed by analyzing data collected by a five-camera, three-dimensional (3-D) motion analysis system. RESULTS. When vision was blurred, subjects took 11% longer to execute the stepping task (P Ͻ 0.05), mediolateral displacement of the point of application of the ground reaction force vector (i.e., weighted average of all pressures over the area in contact with the ground; the so called center of pressure, CP) decreased from 37.6% of stance width to 28.3% (P Ͻ 0.01), maximum distance between the mediolateral position of the CM and CP decreased by 9.8 mm (P Ͻ 0.01), and toe clearance (distance between tip of shoe and edge of step) increased in both the horizontal (28%) and vertical (19%) direction (P Ͻ 0.05). CONCLUSIONS. These findings suggest that when vision was blurred, subjects used a twofold safety-driven adaptation: First, to increase dynamic stability they ensured that the horizontal position of their CM was kept close to the center of the base of support and second, they increased horizontal and vertical toe clearance while swinging their lead limb forward to reduce the risk of tripping. (Invest Ophthalmol Vis Sci

The UK Pharmacy Care Plan service: Description, recruitment and initial views on a new community pharmacy intervention

Introduction: The UK government advocates person-centred healthcare which is ideal for supporting patients to make appropriate lifestyle choices and to address non-adherence. The Community Pharmacy Future group, a collaboration between community pharmacy companies and independents in the UK, introduced a person-centred service for patients with multiple long-term conditions in 50 pharmacies in Northern England. Objective: Describe the initial findings from the set up and delivery of a novel community pharmacy-based person-centred service. Method: Patients over fifty years of age prescribed more than one medicine including at least one for cardiovascular disease or diabetes were enrolled. Medication review and person-centred consultation resulted in agreed health goals and steps towards achieving them. Data were collated and analysed to determine appropriateness of patient recruitment process and quality of outcome data collection. A focus group of seven pharmacists was used to ascertain initial views on the service. Results: Within 3 months of service initiation, 683 patients had baseline clinical data recorded, of which 86.9% were overweight or obese, 53.7% had hypertension and 80.8% had high cardiovascular risk. 544 (77.2%) patients set at least one goal during the first consultation with 120 (22.1%) setting multiple goals. A majority of patients identified their goals as improvement in condition, activity or quality of life. Pharmacists could see the potential patient benefit and the extended role opportunities the service provided. Allowing patients to set their own goals occasionally identified gaps to be addressed in pharmacist knowledge. Conclusion: Pharmacists successfully recruited a large number of patients who were appropriate for such a service. Patients were willing to identify goals with the pharmacist, the majority of which, if met, may result in improvements in quality of life. While challenges in delivery were acknowledged, allowing patients to identify their own personalised goals was seen as a positive approach to providing patient services

Recent Results from Epitaxial Growth on Step Free 4H-SiC Mesas

This paper updates recent progress made in growth, characterization, and understanding of high quality homoepitaxial and heteroepitaxial films grown on step-free 4H-SiC mesas. First, we report initial achievement of step-free 4H-SiC surfaces with carbon-face surface polarity. Next, we will describe further observations of how step-free 4H-SiC thin lateral cantilever evolution is significantly impacted by crystal faceting behavior that imposes non-uniform film thickness on cantilever undersides. Finally, recent investigations of in-plane lattice constant mismatch strain relief mechanisms observed for heteroepitaxial growth of 3C-SiC as well as 2H-AlN/GaN heterofilms on step-free 4H-SiC mesas will be reviewed. In both cases, the complete elimination of atomic heterointerface steps on the mesa structure enables uniquely well-ordered misfit dislocation arrays to form near the heterointerfaces with remarkable lack of dislocations threading vertically into the heteroepilayers. In the case of 3C-SiC heterofilms, it has been proposed that dislocation half-loops nucleate at mesa edges and glide laterally along the step-free 3C/4H interfaces. In contrast, 3C-SiC and 2H-AlN/GaN heterofilms grown on 4H-SiC mesas with steps exhibit highly disordered interface misfit dislocation structure coupled with 100X greater density of dislocations threading through the thickness of the heteroepilayers. These results indicate that the presence of steps at the heteroepitaxial interface (i.e., on the initial heteroepitaxial nucleation surface) plays a highly important role in the defect structure, quality, and relaxation mechanisms of single-crystal heteroepitaxial films

Exploring constituency-level estimates for the 2017 British general election

Most opinion polls conducted during British general election campaigns report on each party’s estimated national vote share. Although of considerable interest, these data do not put the spotlight on the marginal seats, the constituencies targeted by the parties for intensive canvassing; these are where the contest for a majority in the House of Commons is won and lost. There have been some polls covering those constituencies as a whole, but very few of individual constituencies so there was very little reporting of the outcome for each party in those individual constituencies. That changed with the 2017 general election, when three analysts published estimates on the internet of each party’s vote share separately for each constituency and with those data predicted which party would win each seat. This paper explores the veracity of those estimates, finding that although in general terms they accurately represented the relative position of each constituency in the share of each party’s votes, nevertheless their estimates of which marginal seats would be won by each were not as accurate. The implications of such polls, especially as their predictive ability is improved, is discussed

Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors

Evidence for Limited Genetic Compartmentalization of HIV-1 between Lung and Blood

BACKGROUND:HIV-1 is frequently detected in the lungs of infected individuals and is likely important in the development of pulmonary opportunistic infections. The unique environment of the lung, rich in alveolar macrophages and with specialized local immune responses, may contribute to differential evolution or selection of HIV-1. METHODOLOGY AND FINDINGS:We characterized HIV-1 in the lung in relation to contemporaneous viral populations in the blood. The C2-V5 region of HIV-1 env was sequenced from paired lung (induced sputum or bronchoalveolar lavage) and blood (plasma RNA and proviral DNA from sorted or unsorted PBMC) from 18 subjects. Compartmentalization between tissue pairs was assessed using 5 established tree or distance-based methods, including permutation tests to determine statistical significance. We found statistical evidence of compartmentalization between lung and blood in 10/18 subjects, although lung and blood sequences were intermingled on phylogenetic trees in all subjects. The subject showing the greatest compartmentalization contained many nearly identical sequences in BAL sample, suggesting clonal expansion may contribute to reduced viral diversity in the lung in some cases. However, HIV-1 sequences in lung were not more homogeneous overall, nor were we able to find a lung-specific genotype associated with macrophage tropism in V3. In all four subjects in whom predicted X4 genotypes were found in blood, predicted X4 genotypes were also found in lung. CONCLUSIONS:Our results support a picture of continuous migration of HIV-1 between circulating blood and lung tissue, with perhaps a very limited degree of localized evolution or clonal replication