A method for estimating maternal and newborn lives saved from health-related investments funded by the UK government Department for International Development using the Lives Saved Tool.

Background: In 2010, the UK Government Department for International Development (DFID) committed through its 'Framework for results for reproductive, maternal and newborn health (RMNH)' to save 50,000 maternal lives and 250,000 newborn lives by 2015. They also committed to monitoring the performance of this portfolio of investments to demonstrate transparency and accountability. Methods currently available to directly measure lives saved are cost-, time-, and labour-intensive.

Patients' views on topical negative pressure: 'effective but smelly'.

Topical negative pressure (TNP) is increasingly being used in both the UK and internationally, on wounds of acute, chronic and surgical origin. However, little is known about patients' experiences of this therapy. NHS Quality Improvement Scotland undertook a health technology assessment on TNP in 2009-2010.

Cardiovascular risk profiles in UK-born Caribbeans and Irish living in England and Wales.

Cardiovascular disease is the leading cause of morbidity and mortality among Caribbean and Irish origin people living in England and Wales. Yet mortality from coronary heart disease (CHD) of migrant Caribbeans is lower than the national average, while stroke mortality is higher. The Irish experience higher than average mortality from both diseases.

Is going to church good or bad for you? Denomination, attendance and mental health of children in West Scotland.

Religiosity is often associated with mental health in adult populations, but not in a consistent direction. Conflicting results reflect the multidimensional nature of both concepts. Few studies have addressed the relationship between religiosity and mental health among children.

Poor but healthy? The youngest generation of Irish catholics in west Scotland.

Objective: Catholic adults in the West of Scotland, who are mainly of Irish origin, have been shown to suffer excess morbidity and mortality compared to the general population. A major contributing factor to this inequality is socio-economic disadvantage. This paper investigates the health and socio-economic position of Catholics in the youngest generation.

Morbidity and Irish Catholic descent in Britain. Relating health disadvantage to socio-economic position.

In common with some other ethnic and religious minorities whose forebears migrated from their country of origin, Irish Catholics in Britain are less well off than the host population in terms of socio-economic position and health. Results are presented from a Scottish study, where Catholic religion of origin mainly indicates Irish ancestry, and it is estimated that about one-third of the population is of significant Irish descent. In this study, excess of physical and mental health problems and disability have previously been reported for those of Catholic background, particularly in the eldest cohort (aged 56 in 1988), and have not been fully explained by health-related behaviour.

Morbidity and Irish Catholic descent in Britain: relating health disadvantage to behaviour.

Objectives: This paper critically evaluates the evidence for two health-related stereotypes of the Irish, namely that behaviours such as smoking and heavy drinking explain their excess morbidity in Britain, and secondly that, in illness, this ethnic group behaves more stoically.

Design: Data are reported on over 850 respondents from each of three cohorts (aged 18, 39 and 58 in 1990/91) of the West of Scotland 20-07 Study, in which a small but pervasive excess of morbidity has been observed in those of Catholic background (in this area associated with Irish descent). Logistic regression was used to investigate any differences in drinking, smoking and participation in sport between those of Catholic and non-Catholic heritage, whilst controlling for sex and social class.

Association of medical, physiological, behavioural and socio-economic factors with elevated mortality in men of Irish heritage in West Scotland.

Background: Men with patrilineal Irish descent from the immigrations of the nineteenth and twentieth centuries have higher death rates from 'all-causes' and, specifically, cardiovascular disease (CVD) than the general population of the West of Scotland.

Methods: A total of 5766 male employees from 27 workplace settings were examined between 1970 and 1973. Surname analysis identified 15 per cent of these men as of patrilineal Irish heritage.

Mortality in men of Irish heritage in West Scotland.

Britons of Irish parentage have been found to exhibit poorer health and to die at a younger age than the general population. This paper expands the investigation of Irish mortality patterns in Britain, to include men with patrilineal Irish descent from the immigration of the 19th and 20th centuries. Five thousand, seven hundred and sixty-six male employees aged between 35 and 64 y were examined in 27 workplace settings in Glasgow, Grangemouth and Clydebank between 1970 and 1973.

Morbidity and Irish Catholic descent in Britain: an ethnic and religious minority 150 years on.

Ethnic and religious minorities often suffer disadvantages both in socio-economic status and in health. Data from the West of Scotland Twenty-07 study suggest some differences in morbidity between those descended from Irish Catholic migrants of the great emigration from 1840 onwards and others. Catholic religion of at least one parent or at birth is used here as a proxy measure to indicate Irish Catholic descent, on the basis of estimates of sensitivity and specificity in the local area.

Error-prone polymerization by HIV-1 reverse transcriptase. Contribution of template-primer misalignment, miscoding, and termination probability to mutational hot spots.

We have observed previously that DNA template-directed polymerization by the type 1 human immunodeficiency virus reverse transcriptase is error-prone for single-nucleotide substitution, addition and deletion errors at homopolymeric sequences. We have also noted strong termination of processive synthesis at these positions (Bebenek, K., Abbotts, J.

Mechanism of HIV-1 reverse transcriptase. Termination of processive synthesis on a natural DNA template is influenced by the sequence of the template-primer stem.

During processive DNA synthesis in vitro, the human immunoefficiency virus, type 1 (HIV-1) reverse transcriptase encounters template nucleotide positions at which continued synthesis is difficult. At these positions, the enzyme has a relatively high probability of dissociating from the template, and product molecules of corresponding length accumulate as the incubation proceeds. These positions, which are known as termination sites, could be associated with template secondary structures in some cases, but many termination sites appear to be template sequence-related rather than secondary structure-related.

Inhibitors of HIV-1 reverse transcriptase and fidelity of in vitro DNA replication.

Mechanisms of the effects of the dTTP analogues 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) and 3'-amino-3'-deoxythymidine 5'-triphosphate (NH2 TTP) upon the HIV-1 reverse transcriptase (RT) are discussed. These compounds block the RT in vitro and do so by different kinetic mechanisms. Infidelity of replication is a hallmark of the HIV-1 RT, and replication errors by the enzyme on RNA and DNA templates are discussed.

Protein-protein interactions of HIV-1 reverse transcriptase: implication of central and C-terminal regions in subunit binding.

Human immunodeficiency virus 1 reverse transcriptase (RT) purified from virions is composed of a approximately 51,000 Mr polypeptide and a approximately 66,000 Mr polypeptide that are thought to be in heterodimer structure (Chandra et al., 1986; Hansen et al., 1988; Starnes & Cheng, 1989) and are identical except for a 15,000 Mr C-terminal truncation in the smaller species (Di Marzo-Veronese et al.

Thermodynamics of A:G mismatch poly(dG) synthesis by human immunodeficiency virus 1 reverse transcriptase.

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase has been found to conduct error-prone synthesis on DNA and RNA templates. We find here that tolerance of an A:G mispair with poly(rA) as template is particularly strong, such that extensive poly(dG) synthesis is conducted. This type of extensive misincorporation is not observed with several reference DNA polymerases.

Identification and properties of the catalytic domain of mammalian DNA polymerase beta.

Rat DNA polymerase beta (beta-pol) is a 39-kDa protein organized in two tightly folded domains, 8-kDa N-terminal and 31-kDa C-terminal domains, connected by a short protease-sensitive region. The 8-kDa domain contributes template binding to the intact protein, and we now report that the 31-kDa C-terminal domain contributes catalytic activity. Our results show that this domain as a purified proteolytic fragment conducts DNA synthesis under appropriate conditions but the kcat is lower and primer extension properties are different from those of the intact enzyme.

Mechanism of HIV reverse transcriptase: enzyme-primer interaction as revealed through studies of a dNTP analogue, 3'-azido-dTTP.

Primer and dNTP recognition by purified HIV reverse transcriptase have been investigated. Earlier kinetic studies suggested that the reaction pathway for DNA synthesis is ordered, with template-primer and free enzyme combining to form the first complex in the reaction sequence [Majumdar et al. (1988) J.

Specificity and mechanism of error-prone replication by human immunodeficiency virus-1 reverse transcriptase.

DNA-dependent DNA synthesis in vitro by human immunodeficiency virus-1 reverse transcriptase is relatively error-prone. The enzyme, whether recombinant or from virus particles, produces errors while replicating M13mp2 DNA at a rate that, if operative in vivo, would produce about five mutations per genome per round of replication. Sequence analysis of mutants resulting from in vitro synthesis demonstrates that errors are nonrandomly distributed.

Studies on the mechanism of human immunodeficiency virus reverse transcriptase. Steady-state kinetics, processivity, and polynucleotide inhibition.

A study of steady-state kinetics of polymerization by purified human immunodeficiency virus DNA polymerase (reverse transcriptase) has been conducted. DNA synthesis was examined using a system of poly(rA) as template, oligo(dT) as primer, and dTTP as nucleotide substrate. The substrate initial velocity patterns point to an ordered mechanism with template-primer adding first.

Studies on the mechanism of Escherichia coli DNA polymerase I large fragment. Effect of template sequence and substrate variation on termination of synthesis.

Termination of Escherichia coli DNA polymerase I large fragment after processive synthesis on natural and other well-defined template.primer systems has been examined. We found that after any given deoxynucleoside monophosphate incorporation termination occurs in a nonrandom manner with phi X174 DNA as template: Termination is much more likely at some nucleotide residues along the template than at others.

Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme.

The coding region of a human beta-polymerase cDNA, predicting a 335 amino acid protein, was subcloned in the Escherichia coli expression plasmid pRC23. After induction of transformed cells, the crude soluble extract was found to contain a new protein immunoreactive with beta-polymerase antibody and corresponding in size to the protein deduced from the cDNA. This protein was purified in a yield of 1-2 mg/50 g of cells.

On the fidelity of DNA replication: herpes DNA polymerase and its associated exonuclease.

Procaryotic DNA polymerases contain an associated 3'----5' exonuclease activity which provides a proofreading function and contributes substantially to replication fidelity. DNA polymerases of the eucaryotic herpes-type viruses contain similar associated exonuclease activities. We have investigated the fidelity of polymerases purified from wild type herpes simplex virus, as well as from mutator and antimutator strains.

On the fidelity of DNA replication: use of synthetic oligonucleotide-initiated reactions.

The phi X174 fidelity system provides a biological assay for quantitating the accuracy of DNA polymerases. Expansion of this system to cell extracts and DNA replication complexes from eucaryotes has been limited by the presence of nucleases in these preparations. We have overcome these limitations by priming the phi X template with a synthetic oligodeoxynucleotide, with its free 3'-hydroxyl terminus only a short distance from the amber locus that is the site for determining the frequency of misincorporation.