PubMed Health⌕ Search

Biomedical subjects

Michael A Shields

Publications and source records attributed to Michael A Shields.

8 recordsLinked to original sources
PubMed2007

Investigating the quitting decision of nurses: panel data evidence from the British National Health Service.

In this paper, we provide a detailed investigation into the quitting behaviour of nurses in the British National Health Service (NHS), using a recently constructed longitudinal survey. We fit both single and competing risks duration models that enable us to establish the characteristics of those nurses who leave the public sector, distinguish the importance of pay in this decision and document the destinations that nurses move to. Contrary to expectations, we find that the hourly wage received by nurses outside of the NHS is around 20% lower than in the NHS, and that hours of work are about the same. However, while the effect of wages is found to be statistically significant, the predicted impact of an increase in nurses' pay on retention rates is small. The current nurse retention problem in the NHS is therefore unlikely to be eliminated through substantially increased pay.

Adolescent↗
PubMed2006

The child health/family income gradient: Evidence from England.

Recent studies using Canadian and US data have documented a positive relationship between family income and child health, with the slope of the gradient being larger for older than younger children [Case, A., Lubotsky, D., Paxson, C., 2002. Economic status and health in childhood: the origins of the gradient. American Economic Review 92, 1308-1334; Currie, J., Stabile, M., 2003. Socioeconomic status and child health: why is the relationship stronger for older children? American Economic Review 93, 1813-1823]. In this paper we explore whether or not these findings hold for England, analysing a sample of over 13,000 children (and their parents) drawn from the Health Survey for England. While we find consistent and robust evidence of a significant family income gradient in child health, using the subjective general health status measure, the slope of the gradient is very small. Moreover, we find no evidence that the slope of the gradient increases with child age. Furthermore, we find no evidence of such a gradient with more objective measures, based on nurse examinations and blood test results. Together these results suggest that family income is not a major determinant of child health in England. Finally, we provide some evidence that nutrition and family lifestyle choices have an important role in determining child health and that child health is highly correlated within the family.

Adolescent↗
PubMed2005

The causal effect of income on health: evidence from German reunification.

We investigate whether there was a causal effect of income changes on the health satisfaction of East and West Germans in the years following reunification. Our data source is the German Socio-Economic Panel (GSOEP) between 1984 and 2002, and we fit a recently proposed fixed-effects ordinal estimator to our health measures and use a causal decomposition technique to account for panel attrition. We find evidence of a significant positive effect of income changes on health satisfaction, but the quantitative size of this effect is small. This is the case with respect to current income and a measure of 'permanent' income.

Adult↗
PubMed2004

Reovirus oncolysis: the Ras/RalGEF/p38 pathway dictates host cell permissiveness to reovirus infection.

Reovirus is a benign human virus that was recently found to have oncolytic properties and is currently in clinical trials as a potential cancer therapy. We have previously demonstrated that activation of Ras signaling, a common event in cancer, renders cells susceptible to reovirus oncolysis. In this study, we investigate which elements downstream of Ras are important in reovirus infection. By using a panel of NIH 3T3 cells transformed with activated Ras mutated in the effector-binding domain, we found that only the RasV12G37 mutant, which was unable to signal to Raf or phosphatidylinositol 3-kinase but retained signaling capability to guanine nucleotide-exchange factors (GEFs) for the small G protein, Ral (known as RalGEFs), was permissive to reovirus. Expression of the activated mutant of the RalGEF, Rlf, also allowed reovirus replication. Specific inhibition of the Ral pathway by using dominant-negative RalA rendered normally permissive H-Ras cells (cells expressing activated Ras) resistant to reovirus. To further identify elements downstream of RalGEF that promote reovirus infection, we used chemical inhibitors of the downstream signaling elements p38 and JNK. We found that reovirus infection was blocked in the presence of the p38 inhibitor but not the JNK inhibitor. Together, these results implicate a Ras/RalGEF/p38 pathway in the regulation of reovirus replication and oncolysis.

3T3 Cells↗
PubMed2004

UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function through rapid proteolytic degradation.

The p53-inducible gene 3 (PIG3) is a transcriptional target of the tumor suppressor protein p53 and is thought to play a role in apoptosis. In this report, we identify a novel alternatively spliced product from the PIG3 gene that we call PIG3AS (PIG3 alternative splice). PIG3AS results from alternative pre-mRNA splicing that skips exon 4 of the five exons included in the PIG3 transcript. The resulting protein product shares its first 206 amino acids with PIG3 but has a unique 42-amino acid C terminus. In unstressed cells and after most DNA damage conditions that induce transcription from the PIG3 gene, production of the PIG3 transcript dominates. However, in response to UV light, pre-mRNA splicing shifts dramatically in favor of PIG3AS. Unlike the PIG3 protein, the PIG3AS protein is rapidly degraded with a short half-life and is stabilized by proteasome inhibition. Our results illustrate the first example of an endogenous, UV-inducible, alternative splicing event and that control of the splicing machinery is involved in the cellular DNA damage response. They also suggest that rapid proteolytic degradation represents a cellular mechanism for uncoupling p53 activity from PIG3 gene activation that is independent of promoter selectivity.

Alternative Splicing↗
PubMed2004

Does problem drinking affect employment? Evidence from England.

In this paper, we use data from the Health Survey of England to show that problem drinking is negatively and significantly associated with the probability of being in work, once the endogenous relationship between these outcomes is accounted for. Being a problem drinker leads to a substantial reduction in the probability of working by between 7 and 31%, the former figure being roughly equivalent to the positive effect of having a degree relative to no qualifications in our data. This finding is robust to a variety of identifying restrictions and definitions of problem drinking. Moreover, we find that problem drinking defined by the observed psychological and physical symptoms of alcohol is an important predictor of employment, and allows for the fact that individuals differ in their tolerance or susceptibility to alcohol. Our results suggest that there may be important labour market benefits from public health policies aimed at the prevention and treatment of problem drinking.

Alcoholism↗
PubMed2002

Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect.

Precisely how mutant p53 exerts a dominant negative effect over wild type p53 has been an enigma. To understand how wild type and mutant p53 form hetero-oligomers, we studied p53 biogenesis in vitro. We show here that p53 dimers are formed cotranslationally (on the polysome), whereas tetramers are formed posttranslationally (by the dimerization of dimers in solution). Coexpression of wild type and mutant p53 therefore results in 50% of the p53 generated being heterotetramers comprised of a single species: wild type dimer/mutant dimer. Using hot spot mutants of p53 and a variety of natural target sites, we show that all wild type/mutant heterotetramers manifest impaired DNA binding activity. This impairment is not due to the mutant dimeric subunit inhibiting association of the complex with DNA but rather due to the lack of significant contribution (positive cooperativity) from the mutant partner. For all heterotetramers, bias in binding is particularly pronounced against those sequences in genes responsible for apoptosis rather than cell growth arrest. These results explain the molecular basis of p53 dominant negative effect and suggest a functional role in the regulation of p53 tetramerization.

Base Sequence↗