Virus interference and estimates of influenza vaccine effectiveness from test-negative studies

Letterspostprin

Ebola: Worldwide Dissemination Risk and Response Priorities

published_or_final_versio

Case fatality: Rate, ratio, or risk? (letter)

postprin

Sample size considerations for one-to-one animal transmission studies of the influenza A viruses

published_or_final_versio

RAM function is dependent on Kapβ2-mediated nuclear entry

Eukaryotic gene expression is dependent on the modification of the first transcribed nucleotide of pre-mRNA by the addition of the 7-methylguanosine cap. The cap protects transcripts from exonucleases and recruits complexes which mediate transcription elongation, processing and translation initiation. The cap is synthesized by a series of reactions which link 7-methylguanosine to the first transcribed nucleotide via a 5′ to 5′ triphosphate bridge. In mammals, cap synthesis is catalysed by the sequential action of RNGTT (RNA guanylyltransferase and 5′-phosphatase) and RNMT (RNA guanine-7 methyltransferase), enzymes recruited to RNA pol II (polymerase II) during the early stages of transcription. We recently discovered that the mammalian cap methyltransferase is a heterodimer consisting of RNMT and the RNMT-activating subunit RAM (RNMT-activating mini-protein). RAM activates and stabilizes RNMT and thus is critical for cellular cap methylation and cell viability. In the present study we report that RNMT interacts with the N-terminal 45 amino acids of RAM, a domain necessary and sufficient for maximal RNMT activation. In contrast, smaller components of this RAM domain are sufficient to stabilize RNMT. RAM functions in the nucleus and we report that nuclear import of RAM is dependent on PY nuclear localization signals and Kapβ2 (karyopherin β2) nuclear transport protein

Regulation of mRNA capping in the cell cycle

The mRNA cap structure, which is added to nascent RNA pol II transcripts, recruits the protein complexes required for pre-mRNA transcript processing, mRNA export and translation initiation. The enzymes which catalyze mRNA cap synthesis are regulated by cellular signaling pathways which impact on their expression, localization and activity. Here we discuss the recent observation that the mRNA cap methyltransferase, RNMT, is phosphorylated on Thr-77 by CDK1-cyclin B1, which regulates its activity and the proteins with which it interacts. RNMT Thr-77 phosphorylation provides a burst of mRNA cap methyltransferase activity during early G1 phase at a time when transcription is reactivated following completion of the cell cycle. This co-ordination of transcription and mRNA capping makes an important contribution to gene expression in the cell; preventing RNMT Thr-77 phosphorylation inhibits cell proliferation. Here we discuss these findings and how mRNA cap synthesis may be regulated in other scenarios

How Is vaccine effectiveness scaled by the transmission dynamics of interacting pathogen strains with cross- protective immunity?

published_or_final_versio

Potential use of school absenteeism record for disease surveillance in developing countries, case study in rural Cambodia

published_or_final_versio

The association of seasonal influenza vaccination with pandemic influenza H1N1 2009 infection

Letter to the editor; Comment on Vaccine. 2011 Nov 15, v. 29 n. 49, p. 9194-200In 2010 Skowronski and colleagues reported that seasonal influenza vaccine appeared to increase the risk of pandemic influenza H1N1 2009 (pH1N1) infection during the first pandemic wave in Canada [1]. They suggested a number of possible explanations for their unexpected finding: firstly, that the results were an artefact of selection bias or confounding; secondly, that the results were due to partial mediation through a biological mechanism; and thirdly, that the results were due to a direct immune mechanism, such as antibody dependent enhancement [1]. In a recent paper in Vaccine, Rosella and colleagues have investigated in detail the first of these possibilities, confirming that it is unlikely an unidentified confounder could have explained the findings [2]. © 2011 Elsevier Ltd.postprin

Access to primary care and the route of emergency admission to hospital: retrospective analysis of national hospital administrative data

BACKGROUND: The UK government is pursuing policies to improve primary care access, as many patients visit accident and emergency (A and E) departments after being unable to get suitable general practice appointments. Direct admission to hospital via a general practitioner (GP) averts A and E use, and may reduce total hospital costs. It could also enhance the continuity of information between GPs and hospital doctors, possibly improving healthcare outcomes. OBJECTIVE: To determine whether primary care access is associated with the route of emergency admission-via a GP versus via an A and E department. METHODS: Retrospective analysis of national administrative data from English hospitals for 2011-2012. Adults admitted in an emergency (unscheduled) for ≥1 night via a GP or an A and E department formed the study population. The measure of primary care access-the percentage of patients able to get a general practice appointment on their last attempt-was derived from a large, nationally representative patient survey. Multilevel logistic regression was used to estimate associations, adjusting for patient and admission characteristics. RESULTS: The analysis included 2 322 112 emergency admissions (81.9% via an A and E department). With a 5 unit increase in the percentage of patients able to get a general practice appointment on their last attempt, the adjusted odds of GP admission (vs A and E admission) was estimated to increase by 15% (OR 1.15, 95% CI 1.12 to 1.17). The probability of GP admission if ≥95% of appointment attempts were successful in each general practice was estimated to be 19.6%. This probability reduced to 13.6% when <80% of appointment attempts were successful. This equates to 139 673 fewer GP admissions (456 232 vs 316 559) assuming no change in the total number of admissions. Associations were consistent in direction across geographical regions of England. CONCLUSIONS: Among hospital inpatients admitted as an emergency, patients registered to more accessible general practices were more likely to have been admitted via a GP (vs an A and E department). This furthers evidence suggesting that access to general practice is related to use of emergency hospital services in England. The relative merits of the two admission routes remain unclear