Publications by authors named "Laura J Walton"

Article Synopsis
  • Second-generation ALK inhibitors, alectinib and brigatinib, are effective front-line treatments for ALK-positive non-small cell lung cancer, but there are no direct comparisons between the two.
  • The study aimed to compare overall survival (OS) rates for brigatinib versus alectinib using indirect treatment comparisons (ITCs) from two clinical trials, ALEX and ALTA-1L.
  • Results showed that OS rates for both drugs were comparable, regardless of the analysis method, suggesting no significant difference in survival between the two treatments for patients new to ALK inhibitors.
View Article and Find Full Text PDF

To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive -positive non-small-cell lung cancer (NSCLC). Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases.

View Article and Find Full Text PDF

This article challenges the use of hyperoxia in the perioperative period. It describes the biochemical and physiologic basis for both the direct and indirect adverse effects of oxygen. The reasons for using hyperoxia in the perioperative period are critically evaluated, and the evidence and guidelines for oxygen use in common acute medical conditions are reviewed.

View Article and Find Full Text PDF

The ability of certain plants, invertebrates, and microorganisms to survive almost complete loss of water has long been recognized, but the molecular mechanisms of this phenomenon remain to be defined. One phylogenetically widespread adaptation is the presence of abundant, highly hydrophilic proteins in desiccation-tolerant organisms. The best characterized of these polypeptides are the late embryogenesis abundant (LEA) proteins, first described in plant seeds >20 years ago but recently identified in invertebrates and bacteria.

View Article and Find Full Text PDF

The biosynthetic pathway to 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC), a key intermediate in the biosynthesis of prodiginine antibiotics in Streptomyces coelicolor, has been elucidated using a combination of gene replacements and feeding experiments with chemically synthesised MBC and a synthetic analogue of a pathway intermediate.

View Article and Find Full Text PDF

Studies in anhydrobiotic plants have defined many genes which are upregulated during desiccation, but comparable studies in invertebrates are at an early stage. To develop a better understanding of invertebrate anhydrobiosis, we have begun to characterise dehydration-inducible genes and their proteins in anhydrobiotic nematodes and bdelloid rotifers; this review emphasises recent findings with a hydrophilic nematode protein. Initial work with the fungivorous nematode Aphelenchus avenae led to the identification of two genes, both of which were markedly induced on slow drying (90-98% relative humidity, 24 hr) and also by osmotic stress, but not by heat or cold or oxidative stresses.

View Article and Find Full Text PDF

Several polyketide secondary metabolites are shown by feeding experiments to incorporate glycerol-derived 3-carbon starter units, 2-carbon extender units, or 3-carbon branches into their hydrocarbon chains. In recent years, genetic studies have begun to elucidate the mechanisms by which this occurs. In this article we review the incorporation of glycerol-derived precursors into polyketides and propose new mechanisms for the incorporation processes.

View Article and Find Full Text PDF

LEA (late embryogenesis abundant) proteins in both plants and animals are associated with tolerance to water stress resulting from desiccation and cold shock. However, although various functions of LEA proteins have been proposed, their precise role has not been defined. Recent bioinformatics studies suggest that LEA proteins might behave as molecular chaperones, and the current study was undertaken to test this hypothesis.

View Article and Find Full Text PDF