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 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 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 −12% to 31%) against infant ear disease and 30% (95% CI −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 −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

Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

Background: Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. Methods: We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.Results: We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. Conclusions: PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months

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

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

Skilled But Unaware of It: Occurrence and Potential Long-Term Effects of Females' Financial Underconfidence

We find strong gender- and education-related differences in the distribution of actual and perceived financial sophistication: Whereas financial literacy rises in formal education, confidence increases in education for men but decreases for women. We show that the financial decisions of highly-educated men benefit strongly from this excess confidence, while the underconfidence of highly-educated women, in contrast, impairs their long-term financial planning

Stock market literacy, trust, and participation

This article studies the importance of stock market literacy and trust for stock ownership decisions. We find that these two distinct channels simultaneously explain not only the probability of participation, but, conditional on participation, also explain the share of investment in stocks. Once we account for stock market literacy, sociability is no longer significant for participation; what matters is literacy rather than sociability. Further, we observe that economic shocks and future expectations are key behavioral characteristics that explain a household’s decision to invest in stocks. However, upon participation, a larger set of behavioral characteristics explains the level of stock investment