Measuring the difference between actual and reported food intakes in the context of energy balance under laboratory conditions

Acknowledgements The present study was funded by the Food Standards Agency, UK. The Food Standards Agency had no role in the design, analysis or writing of this article. The authors’ responsibilities were as follows: R. J. S., L. M. O’R. and G. W. H. designed the research; L. M. O’R. and Z. F. conducted the research and analysed the data; G. W. H. performed the statistical analyses; P. R. carried out the DLW analysis; R. J. S. had primary responsibility for the final content; R. J. S., L. M. O’R., Z. F., S. W. and M. B. E. L. wrote the paper.Peer reviewedPublisher PD

Assessing the reactivity of sodium alkyl-magnesiates towards quinoxaline : single electron transfer (SET) vs. nucleophilic alkylation processes

By exploring the reactivity of sodium butyl-magnesiate (1) supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}(2-) (Ar* = 2,6-iPr2-C6H3) towards Quinoxaline (Qx), the ability of this bimetallic system to effectively promote SET processes has been disclosed. Thus 1 executes the single-electron reduction of Qx affording complex (2) whose structure in the solid state contains two quinaxolyl radical anions Qx˙ stabilised within a dimeric magnesiate framework. Combining multinuclear NMR and EPR measurements with DFT calculations, new insights into the constitution of 2 in solution and its magnetic behaviour have been gained. Further evidence on the SET reactivity of 1 was found when it was reacted with nitroxyl radical TEMPO which furnished contacted ion pair sodium magnesiate [(Ph2Si(NAr*)2)Mg(TEMPO(-))Na(THF)3] (4) where both metals are connected by an alkoxide bridge, resulting from reduction of TEMPO. The role that the different ligands present in 1 can play in these new SET reactions has also been assessed. Using an amination approach, the Bu group in 1 can be replaced by the more basic amide TMP allowing the isolation of (3) which was characterised by multinuclear NMR and X-ray crystallography. (1)H NMR monitoring of the reaction of 3 with Qx showed its conversion to 2, leaving the hydrogen atoms of the heterocycle untouched. Contrastingly, using sodium homoalkyl magnesiate [NaMg(CH2SiMe3)3] (5) led to the chemoselective C2 alkylation of this heterocycle, suggesting that the presence of the steric stabiliser {Ph2Si(NAr*)2}(2-) on the mixed-metal reagent is required in order to facilitate the Qx reduction

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe

Novel N-heterocyclic activations mediated by magnesium reagents having sterically hindered ligands

Building on recent advances on the synthesis of homometallic Mg compounds bearing highly sterically demanding ligands, but going significantly beyond the state-of-the-art, this thesis report focuses on the synthesis of new sodium magnesiates and magnesium reagents supported by bulky N-chelating ligands {Ph2Si(NAr*)2}2- and {Ar*N=C(Me)CH(Me)NAr*}- (nacnac) as well as their exploitation within the areas of deprotonative metallation, heterocyclic activation and catalytic application in hydroamination reactions of organic heterocumulenes. Firstly, a series of novel sodium magnesiates bearing the sterically demanding bis(amido)silyl ligand {Ph2Si(NAr*)2}2- (Ar*= 2,6-i-Pr2-C6H3) has been prepared. Thus alkyl derivatives [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(R)(THF)}-] (R= Bu, 2; CH2SiMe3, 5) have been synthesised and isolated as crystalline solids by reacting bis(amine)silyl [Ph2Si(NHAr*)2] 1 with the relevant sodium magnesiate NaMg(Bu)R2 (prepared in situ by co-complexation of BuNa with the relevant magnesium alkyl MgR2). In addition, compound 5 has been used as a precursor for the synthesis of a new series of amido sodium magnesiates [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(NR2)(THF)x}-] (NR2 = HMDS, x=1, 6; NR2= NPh2, x=1, 7; NR2 = NiPr2, x=1, 8; NR2 = DMP, x=1, 9; NR2 = TMP, x=0, 10). The reactions of NH2Ar* and pyrrole with complex 5 led to the formation of mixed-metal complexes [{Na(THF)6}+{(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}-] 11 and [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] 12 respectively. Reactivity studies disclosed that TMP derivative 10 was able to carry out the α-magnesiation of thiophene to yield [{Na(THF)6}+{Ph2Si(NAr*)2)Mg(C4H3S)(THF)}-] 13. In moving to reactivity studies with 1,3 benzoazoles complex 2 promotes the chemeoselective magnesiation of methylbenzimidazole (MeBIm) to yield [{Na(THF)5}2+{(Ph2Si(NAr*)2)Mg(MeBIm*)}2-] 14 (MeBIm* = methylbenzimidazolyl), analysis of bond parameters, NMR data and DFT studies suggest that N-methylbenzimidazolyl ligand displays a metal carbene character.;The reaction of 2 with benzothiazole (Btz) promotes a unique activation process of this heterocycle initiating an unprecedented cascade of reactions, where the initial magnesiation of Btz is followed by an intricate sequence of C-C coupling, ring opening, benzothiazolyl insertion into a C=N bond and intramolecular deprotonation leading to the ring opening and functionalisation of three Btz molecules resulting in novel sodium magnesiate [L2Mg2Na2(THF)5] 15. Extending these studies to the diazine molecule quinoxaline allows the synergic entrapment of radical anion (Qox) in the form of dimer [{Na(THF)6}2+{(Ph2Si(NAr*)2)Mg(Qox)}2-] 20 resulting from the homoleptic cleavage of Mg-C bond in the alkyl precursor 2. EPR studies show that 20 is diamagnetic in the solid-state dimeric structure. Homometallic magnesium species [(Dippnacnac)Mg(Bu)(THF)] 22 and [(Dippnacnac)Mg(TMP)] 23 were prepared and structurally defined and their reactivity towards 1,3-benzoazoles has been assessed. Reactions of 22 and 23 with benzoxazole allowed the isolation in both cases of [(Dippnacnac)Mg{O(o-C6H4)NC}(THF)] 24 resulting from ring cleavage of benzoxazolyl anion. Benzothiazole (Btz) was magnesiated at the C2 position by the amido derivative to form [{(Dippnacnac)Mg(Btz*)}2] 25 (Btz*= 2-benzothiazolyl), however when 22 was reacted with Btz a novel activation of Btz occurred in a cascade reaction involving magnesiation, C-C coupling and ring opening resulting in [(Dippnacnac)Mg{(Btz*)C(H)=N(2-C6H4-1-S)}] 26. Complex 23 when reacted with nitrogen derivative methylbenzimidazole (MeBIm) promotes the magnesiation at the C2 position to yield [{(Dippnacnac)Mg(MeBIm*)}2] 27. In contrast alkyl derivative 22 only coordinated to MeBIm through the lone pair on the N to yield [(Dippnacnac)Mg(Bu)(MeBIm)] 28. Studies assessing the catalytic ability of sodium magnesiates to promote the hydroamination of isocyanates and carbodiimides, show that homoleptic [NaMg(CH2SiMe3)2] 32 can effectively catalyse at room temperature the reactions of HNPh2 with several aliphatic isocyanates to yield the relevant ureas [(NHR)C(=O)(NPh2)] (R = tBu, 29, R = Cy, 39, R = Et, 43) in yields ranging from 99 to 100%. Similarly tris(amido) complex [NaMg(NPh2)3] 30 catalyses the trimerisation of aryl isocyanates under mild reaction conditions. The isolation of key intermediates of the stoichiometric reactions provided important information to propose a possible catalytic cycle. Guanidines [(NHR)C(=NR)NPh2] (R =Cy, 48, R = iPr, 49) could be prepared in good-moderate yields (64-65%) by reacting NHPh2 with RN=C=NR using 30 as a catalyst.Building on recent advances on the synthesis of homometallic Mg compounds bearing highly sterically demanding ligands, but going significantly beyond the state-of-the-art, this thesis report focuses on the synthesis of new sodium magnesiates and magnesium reagents supported by bulky N-chelating ligands {Ph2Si(NAr*)2}2- and {Ar*N=C(Me)CH(Me)NAr*}- (nacnac) as well as their exploitation within the areas of deprotonative metallation, heterocyclic activation and catalytic application in hydroamination reactions of organic heterocumulenes. Firstly, a series of novel sodium magnesiates bearing the sterically demanding bis(amido)silyl ligand {Ph2Si(NAr*)2}2- (Ar*= 2,6-i-Pr2-C6H3) has been prepared. Thus alkyl derivatives [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(R)(THF)}-] (R= Bu, 2; CH2SiMe3, 5) have been synthesised and isolated as crystalline solids by reacting bis(amine)silyl [Ph2Si(NHAr*)2] 1 with the relevant sodium magnesiate NaMg(Bu)R2 (prepared in situ by co-complexation of BuNa with the relevant magnesium alkyl MgR2). In addition, compound 5 has been used as a precursor for the synthesis of a new series of amido sodium magnesiates [{Na(THF)6}+{(Ph2Si(NAr*)2)Mg(NR2)(THF)x}-] (NR2 = HMDS, x=1, 6; NR2= NPh2, x=1, 7; NR2 = NiPr2, x=1, 8; NR2 = DMP, x=1, 9; NR2 = TMP, x=0, 10). The reactions of NH2Ar* and pyrrole with complex 5 led to the formation of mixed-metal complexes [{Na(THF)6}+{(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}-] 11 and [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] 12 respectively. Reactivity studies disclosed that TMP derivative 10 was able to carry out the α-magnesiation of thiophene to yield [{Na(THF)6}+{Ph2Si(NAr*)2)Mg(C4H3S)(THF)}-] 13. In moving to reactivity studies with 1,3 benzoazoles complex 2 promotes the chemeoselective magnesiation of methylbenzimidazole (MeBIm) to yield [{Na(THF)5}2+{(Ph2Si(NAr*)2)Mg(MeBIm*)}2-] 14 (MeBIm* = methylbenzimidazolyl), analysis of bond parameters, NMR data and DFT studies suggest that N-methylbenzimidazolyl ligand displays a metal carbene character.;The reaction of 2 with benzothiazole (Btz) promotes a unique activation process of this heterocycle initiating an unprecedented cascade of reactions, where the initial magnesiation of Btz is followed by an intricate sequence of C-C coupling, ring opening, benzothiazolyl insertion into a C=N bond and intramolecular deprotonation leading to the ring opening and functionalisation of three Btz molecules resulting in novel sodium magnesiate [L2Mg2Na2(THF)5] 15. Extending these studies to the diazine molecule quinoxaline allows the synergic entrapment of radical anion (Qox) in the form of dimer [{Na(THF)6}2+{(Ph2Si(NAr*)2)Mg(Qox)}2-] 20 resulting from the homoleptic cleavage of Mg-C bond in the alkyl precursor 2. EPR studies show that 20 is diamagnetic in the solid-state dimeric structure. Homometallic magnesium species [(Dippnacnac)Mg(Bu)(THF)] 22 and [(Dippnacnac)Mg(TMP)] 23 were prepared and structurally defined and their reactivity towards 1,3-benzoazoles has been assessed. Reactions of 22 and 23 with benzoxazole allowed the isolation in both cases of [(Dippnacnac)Mg{O(o-C6H4)NC}(THF)] 24 resulting from ring cleavage of benzoxazolyl anion. Benzothiazole (Btz) was magnesiated at the C2 position by the amido derivative to form [{(Dippnacnac)Mg(Btz*)}2] 25 (Btz*= 2-benzothiazolyl), however when 22 was reacted with Btz a novel activation of Btz occurred in a cascade reaction involving magnesiation, C-C coupling and ring opening resulting in [(Dippnacnac)Mg{(Btz*)C(H)=N(2-C6H4-1-S)}] 26. Complex 23 when reacted with nitrogen derivative methylbenzimidazole (MeBIm) promotes the magnesiation at the C2 position to yield [{(Dippnacnac)Mg(MeBIm*)}2] 27. In contrast alkyl derivative 22 only coordinated to MeBIm through the lone pair on the N to yield [(Dippnacnac)Mg(Bu)(MeBIm)] 28. Studies assessing the catalytic ability of sodium magnesiates to promote the hydroamination of isocyanates and carbodiimides, show that homoleptic [NaMg(CH2SiMe3)2] 32 can effectively catalyse at room temperature the reactions of HNPh2 with several aliphatic isocyanates to yield the relevant ureas [(NHR)C(=O)(NPh2)] (R = tBu, 29, R = Cy, 39, R = Et, 43) in yields ranging from 99 to 100%. Similarly tris(amido) complex [NaMg(NPh2)3] 30 catalyses the trimerisation of aryl isocyanates under mild reaction conditions. The isolation of key intermediates of the stoichiometric reactions provided important information to propose a possible catalytic cycle. Guanidines [(NHR)C(=NR)NPh2] (R =Cy, 48, R = iPr, 49) could be prepared in good-moderate yields (64-65%) by reacting NHPh2 with RN=C=NR using 30 as a catalyst

Community pharmacy personnel interventions for smoking cessation (Review)

A C K N O W L E D G E M E N T S Amanda Lee provided statistical advice. Our thanks to previous authors: Hazel Sinclair and Lindsay Stead. We would also like to thank Rachna Begh and Ali Albasri for peer review, and Sandra Wilcox for performing consumer review. This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure and Cochrane Programme Grant funding to the Cochrane Tobacco Addiction Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health and Social Care. S O U R C E S O F S U P P O R T Internal sources • University of Aberdeen, UK. • Nuffield Department of Primary Care Health Sciences, University of Oxford, UK. External sources • NIHR Cochrane Infrastructure Grant, UK. • NIHR Cochrane Programme Grant, UK.Peer reviewedPublisher PD

New insights into addition reactions of dialkylzinc reagents to trifluoromethyl ketones : structural authentication of a beta-hydride elimination product containing a tetranuclear zinc chain

A systematic study of the stoichiometric alkylation reactions of 2,2,2-trifluoroacetophenone 1 with [ZnR2(TMEDA)] (R = Me, Et, Bu-t, CH2SiMe3; TMEDA = N, N, N', N'-tetramethylethylenediamine) monitored by H-1 and F-19 NMR spectroscopy is presented. For R = Me, Et the alkylation products alkyl(alkoxides) [(TMEDA)Zn(R){OC(CF3)(R)Ph}] (R = Me, 2: Et, 3) are obtained as the single products of the reaction. When the steric bulk of the dialkylzinc reagent is increased the alkylation reaction is inhibited. Thus, for R = Bu-t, the reduction product [(TMEDA)Zn(Bu-t){OC(CF3)(H)Ph}] is obtained as a result of beta-hydride elimination from one of the tBu groups of the organometallic reagent. H-1 NMR spectroscopic monitoring of the reaction allowed the detection of isobutene as a side product of this reduction process. For the highly sterically demanding group R = CH2SiMe3 which lacks hydrogen atoms at the beta position, no reaction is observed even under refluxing conditions. Two important intermediates from these reactions have been structurally elucidated: [(TMEDA)Zn(Me){OC(CF3)(Me)Ph}] (2) which could be involved in the previously reported alkylation reaction of trifluoromethyl ketones by ZnR2 catalysed by TMEDA and unprecedented tetranuclear [(Bu-t)(2)Zn-4{OC(CF3)(H)Ph}(6)] (5) resulting from the reduction of 1 when reacted with (Bu2Zn)-Bu-t, which displays a rare Zn...Zn...Zn...Zn linear chain arrangement for a zinc alkyl(alkoxide)

Magnesium-mediated benzothiazole activation : a room temperature cascade of C-H deprotonation, C-C coupling, ring-opening and nucleophilic addition reactions

Ligand domin(o)ated: In contrast to the straightforward deprotonation of benzothiazole using Grignard reagents, treatment of benzothiazole with 1 leads to a novel type of activation. The initial magnesiation initiates an unstoppable domino reaction of CC coupling, ring opening, nucleophilic addition, and deprotonation to give 2. THF=tetrahydrofuran

Community pharmacy personnel interventions for smoking cessation

Background Community pharmacists could provide effective smoking cessation treatment because they offer easy access to members of the community. They are well placed to provide both advice on the correct use of smoking cessation products and behavioural support to aid smoking cessation. Objectives To assess the effectiveness of interventions delivered by community pharmacy personnel to assist people to stop smoking, with or without concurrent use of pharmacotherapy. Search methods We searched the Cochrane Tobacco Addiction Group Specialised Register, along with clinicaltrials.gov and the ICTRP, for smoking cessation studies conducted in a community pharmacy setting, using the search terms pharmacist* or pharmacy or pharmacies. Date of the most recent search: January 2019. Selection criteria Randomised controlled trials of interventions delivered by community pharmacy personnel to promote smoking cessation amongst their clients who were smokers, compared with usual pharmacy support or any less intensive programme. The main outcome measure was smoking cessation rates at six months or more after the start of the intervention. Data collection and analysis We used standard methodological procedures expected by Cochrane for study screening, data extraction and management. We conducted a meta-analysis using a Mantel-Haenszel random-effects model to generate risk ratios (RRs) and 95% confidence intervals (CIs). Main results We identified seven studies including 1774 participants. We judged three studies to be at high risk of bias and four to be at unclear risk. Each study provided face-to-face behavioural support delivered by pharmacy staff, and required pharmacy personnel training. Typically such programmes comprised support starting before quit day and continuing with weekly appointments for several weeks afterwards. Comparators were either minimal or less intensive behavioural support for smoking cessation, typically comprising a few minutes of one-off advice on how to quit. Participants in both intervention and control arms received equivalent smoking cessation pharmacotherapy in all but one study. All studies took place in high-income countries, and recruited participants visiting pharmacies. We pooled six studies of 1614 participants and detected a benefit of more intensive behavioural smoking cessation interventions delivered by community pharmacy personnel compared with less intensive cessation interventions at longest follow-up (RR 2.30, 95% CI 1.33 to 3.97; I = 54%; low-certainty evidence). Authors' conclusions Community pharmacists can provide effective behavioural support to people trying to stop smoking. However, this conclusion is based on low-certainty evidence, limited by risk of bias and imprecision. Further research could change this conclusion

Isomeric and chemical consequences of the direct magnesiation of 1,3-benzoazoles using β-diketiminate-stabilized magnesium bases

Opening-up new synthetic applications of beta-diketiminate stabilised magnesium complexes, this case study compares the ability of the alkyl [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(THF)] (1) and the amido reagent [{Ar*NC(Me)CHC(Me)NAr*}Mg(TMP)] (2) (Ar* = 2,6-i- Pr-2-C6H3) to promote direct Mg-H exchange towards the series of 1,3-benzoazoles: benzoxazole (boz), benzothiazole (btz) and N-methyl benzimidazole (blm(Me)). Both reagents deprotonate boz at room temperature to yield [{Ar*NC(Me)CHC(Me)NAr*} Mg{O(o-C6H4) NC}(THF)] (3) via the C-O bond cleavage of a putative C2-magnesiated-benzoxazolyl intermediate. Structurally tracking the reactivity of 1 and 2 towards less acidic btz and blm(Me) showed that the behaviour of reagents 1 and 2 diverged dramatically. Kinetically activated TMP-reagent 2 effectively promotes the deprotonative magnesiation of btz and blm(Me) under mild reaction conditions, giving the alpha-metallated intermediates [{Ar* NC(Me) CHC(Me)NAr*}(2)Mg-2{btz*}(2)] (4) and [{Ar*NC(Me)CHC(Me)NAr*}(2)Mg-2{blm(Me)*}(2)] (7) (btz* = 2-benzothiazolyl; blm(Me)* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data revealed that in 4 and 7 the metallated carbon atoms display a markedly carbenic character and that in solution these species exist at room temperature solely as the ring-closed products, without any observable equilibration to the acyclic isomers. Contrastingly, alkyl reagent 1 decreases the magnesiation rate of btz facilitating an intriguing new cascade activation process of two molecules of substrate involving a sequence of deprotonation/coordination/C-C coupling and ring-opening reactions to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{(btz*)C(H)]=N(o-C6H4) S}] (5). Hydrolysis of 5 followed by addition of the radical oxidant TEMPO ultimately produces the homocoupled product bis(benzothiazole) 6 in a 72% isolated yield. Thus, this establishes a novel transition-metal-free method to prepare homocoupled thiazoles. More straightforwardly, the coordination product [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(blm(Me))] (8) was obtained when equimolar amounts of blm(Me) and 1 were reacted, illustrating the kinetic stubbornness of the Mg-C bond in butyl derivative 1. Complex 8 can be envisaged as a valuable guide to the constitution of a premetallation complex (in relation to the complex-induced proximity effect, CIPE)