Structural elaboration of the surprising ortho-zincation of benzyl methyl ether

Breaking with convention, the reaction of the sodium zincate, [(TMEDA)Na(μ-TMP)(μ-tBu)Zn(tBu)] with benzyl methyl ether (PhCH2OMe) produces exclusively an ortho-zincated intermediate [(TMEDA)Na(μ-TMP)(μ-C6H4CH2OMe)Zn(tBu)] instead of the expected 'thermodynamic' α-metallated product

Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.

Streptococcus pneumonia (the pneumococcus) is the leading vaccine preventable cause of serious infections in infants under 5 years of age. The major correlate of protection for pneumococcal infections is serotype-specific IgG antibody. More recently, antibody-independent mechanisms of protection have also been identified. Preclinical studies have found that IL-17 secreting CD4+ Th17 cells in reducing pneumococcal colonisation. This study assessed IL-17A levels in children from Fiji with high and low pneumococcal carriage density, as measured by quantitative real-time PCR (qPCR). We studied Th17 responses in 54 children who were designated as high density carriers (N=27, >8.21x10(5) CFU/ml) or low density carriers (N=27, <1.67x10(5) CFU/ml). Blood samples were collected, and isolated peripheral blood mononuclear cells (PBMCs) were stimulated for 6 days. Supernatants were harvested for cytokine analysis by multiplex bead array and/or ELISA. Th17 cytokines assayed included IL-17A, IL-21, IL-22 as well as TNF-α, IL-10, TGF-β, IL-6, IL-23 and IFNγ. Cytokine levels were significantly lower in children with high density pneumococcal carriage compared with children with low density carriage for IL-17A (p=0.002) and IL-23 (p=0.04). There was a trend towards significance for IL-22 (p=0.057) while no difference was observed for the other cytokines. These data provide further support for the role of Th17-mediated protection in humans and suggest that these cytokines may be important in the defence against pneumococcal carriage

Synthesis of an alkylmagnesium amide and interception of a ring-opened isomer of the important utility amide 2,2,6,6-tetramethylpiperidide (TMP)

Two new magnesium complexes containing the important utility amide 2,2,6,6-tetramethylpiperidide (TMP) have been synthesised. Treating the magnesium bis(alkyl) reagent (Me3SiCH2)2Mg with a molar equivalent of TMP(H) in hydrocarbon medium produces the dimeric alkylmagnesium amide complex [(Me3SiCH2)Mg(μ-TMP)]22, which was isolated in high yield. X-ray crystallography revealed that 2 was an unsymmetrical dimer as unusually the two TMP ligands adopt different conformations – one a chair, the other a twisted boat. Solution studies (multinuclear NMR and DOSY NMR spectroscopies) show that 2 undergoes a monomerisation and Schlenk equilibrium in d8-THF. When (Me3SiCH2)2Mg was reacted with two molar equivalents of TMP(H) in hydrocarbon medium [in an effort to prepare Mg(TMP)2] a crystalline sample of a surprising product, a tetranuclear triheteroanionic amide-alkoxide-amidoalkene [(TMP)Mg(μ-TMP){μ-N(H)C(Me)2CH2CH2CH2C(Me) = CH2}Mg(μ-OCH2SiMe3)]23 was obtained. Complex 3 contains two unexpected anions, namely the alkoxide produced via oxygen insertion into a Mg–C bond, and the primary amidoalkene which is produced via ring opening of the TMP anion

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia

BackgroundWe assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.MethodsIn an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17&ndash;39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30&ndash;36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.ResultsThe consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI &minus;12% to 31%) against infant ear disease and 30% (95% CI &minus;34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI &minus;2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.ConclusionsIn a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs

Resourcefulness, reciprocity and reflexivity: the three Rs of partnership in sport for public health research

This paper explores the dynamics of research–policy–practice (RPP) partnerships in sport. Such partnerships, involving a diverse range of groups, have emerged as a response to: (1) a contemporary political prioritisation in the use of sport for health and wellbeing and (2) a parallel requirement for robust evidence of effectiveness and cost-effectiveness. A conceptual framework for understanding such RPP partnerships is proposed and discussed in relation to three overlapping characteristics; resourcefulness, reciprocity and reflexivity. The paper concludes that understanding these three Rs of RPP partnerships is a way to demythologise the role of sport in public health and present theoretically informed analyses about processes of knowledge production, dissemination and use. It is a conceptual framework which might also further an understanding of, and make public, issues concerning the legitimation of some forms of evidence over others, and potentially maximise the impact of the co-production of knowledge about sport for public health and wellbeing

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to 99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries

Educational paper: Primary antibody deficiencies

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs

Educational paper: The expanding clinical and immunological spectrum of severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities

Research-policy partnerships - experiences of the Mental Health and Poverty Project in Ghana, South Africa, Uganda and Zambia

Background: Partnerships are increasingly common in conducting research. However, there is little published evidence about processes in research-policy partnerships in different contexts. This paper contributes to filling this gap by analysing experiences of research-policy partnerships between Ministries of Health and research organisations for the implementation of the Mental Health and Poverty Project in Ghana, South Africa, Uganda and Zambia. Methods: A conceptual framework for understanding and assessing research-policy partnerships was developed and guided this study. The data collection methods for this qualitative study included semi-structured interviews with Ministry of Health Partners (MOHPs) and Research Partners (RPs) in each country. Results: The term partnership was perceived by the partners as a collaboration involving mutually-agreed goals and objectives. The principles of trust, openness, equality and mutual respect were identified as constituting the core of partnerships. The MOHPs and RPs had clearly defined roles, with the MOHPs largely providing political support and RPs leading the research agenda. Different influences affected partnerships. At the individual level, personal relationships and ability to compromise within partnerships were seen as important. At the organisational level, the main influences included the degree of formalisation of roles and responsibilities and the internal structures and procedures affecting decision-making. At the contextual level, political environment and the degree of health system decentralisation affected partnerships. Conclusions: Several lessons can be learned from these experiences. Taking account of influences on the partnership at individual, organisation and contextual/system levels can increase its effectiveness. A common understanding of mutually-agreed goals and objectives of the partnership is essential. It is important to give attention to the processes of initiating and maintaining partnerships, based on clear roles, responsibilities and commitment of parties at different levels. Although partnerships are often established for a specific purpose, such as carrying out a particular project, the effects of partnership go beyond a particular initiative