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PubMed2002

Partnership for sustainable healthy workplaces: Warner Lecture, British Occupational Hygiene Society, Sheffield 9 April 2002.

The paper sets out a fresh approach to healthy workplaces, laying foundations to meet the demands of the new millennium. Professionals such as occupational hygienists deal with issues at the heart of the economy and society, which are beginning to attract the attention of politicians. Old disciplinary barriers must be crossed and communication improved so that healthy work is accepted as a mainstream concern, integral to sustainable development. This presents challenges both to professionals and to those with responsibilities for policy. As a first step, we need to develop an understanding of how conclusions from research can inform responsible decision making. We will not be able to design and build perfectly safe environments, but real progress can be made in the field of 'workplace health defence', using available human, technical and financial resources. A vital ingredient is partnership in the workplace, involving social partners and professionals working in collaboration.

Employment↗
PubMed1998

The perception of phantom limbs. The D. O. Hebb lecture.

Almost everyone who has a limb amputated will experience a phantom limb--the vivid impression that the limb is not only still present, but in some cases, painful. There is now a wealth of empirical evidence demonstrating changes in cortical topography in primates following deafferentation or amputation, and this review will attempt to relate these in a systematic way to the clinical phenomenology of phantom limbs. With the advent of non-invasive imaging techniques such as MEG (magnetoencephalogram) and functional MRI, topographical reorganization can also be demonstrated in humans, so that it is now possible to track perceptual changes and changes in cortical topography in individual patients. We suggest, therefore, that these patients provide a valuable opportunity not only for exploring neural plasticity in the adult human brain but also for understanding the relationship between the activity of sensory neurons and conscious experience. We conclude with a theory of phantom limbs, some striking demonstrations of phantoms induced in normal subjects, and some remarks about the relevance of these phenomena to the question of how the brain constructs a 'body image.'

Adult↗
PubMed2007

Gordon Holmes Lecture: Gordon Holmes and the neurological heritage.

Sir Gordon Holmes is one of the great figures in the history of twentienth century neurology. In him, there came together the traditions of German and British neurology which moulded a physiological approach to normal and disordered function of the nervous system with a commitment to interpreting clinical phenomena in the light of meticulous pathological examination. He, more than any other individual, was responsible for the form of the neurological examination as it is now performed; and his insights are fundamental to the way that, nowadays, we think about vision, somato-sensory function, the spinal cord and the cerebellum.

Cerebellum↗
PubMed1998

The 1997 Garrod Lecture. The subtleties of antibiotic resistance.

Although the qualitative aspects of antibiotic resistance are increasingly well understood, our understanding of the quantitative aspects has always lagged. Deficiency of understanding or of investigation affects the methods used to characterize the phenotypes of organisms from clinical sources, delays acquisition of knowledge of the importance of quantitative diversity in patient management, and introduces error into epidemiological studies of the prevalence of resistance. This, in turn, gives rise to a devaluation of the work done in diagnostic laboratories in relation to the technology of sensitivity testing, to the interpretation of their results for clinicians, including those used in clinical trials, and to the statistical analyses of resistance trends used inter alia as a guide to empirical antibiotic therapy and to test the efficacy of methods of control. There is a need to bring about a shift of opinion of those who provide funds, in relation to the role of clinical microbiologists and infectious diseases clinicians in defining and solving these problems.

Anti-Bacterial Agents↗
PubMed1999

The 1998 Garrod lecture. Current and future antifungal therapy: new targets for antifungal agents.

Invasive fungal infections are a major problem in immunocompromised patients. The recent expansion of antifungal drug research has occurred because there is a critical need for new antifungal agents to treat these life-threatening invasive infections. The overview of the development of antifungal therapy which is provided herein reflects the increased interest in this very special area of infectious diseases. Although we have newer, less toxic, antifungal agents that are available for clinical use, their clinical efficacy in some invasive fungal infections, such as aspergillosis and fusariosis, is not optimal. Thus, intense efforts in antifungal drug discovery are still needed to develop more promising and effective antifungal agents for use in the clinical arena.

Antifungal Agents↗
PubMed2002

The 2000 Garrod lecture. Factors impacting on the problem of antibiotic resistance.

Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Confronted by increasing amounts of antibiotics over the past 60 years, bacteria have responded to the deluge with the propagation of progeny no longer susceptible to them. While it is clear that antibiotics are pivotal in the selection of bacterial resistance, the spread of resistance genes and of resistant bacteria also contributes to the problem. Selection of resistant forms can occur during or after antimicrobial treatment; antibiotic residues can be found in the environment for long periods of time after treatment. Besides antibiotics, there is the mounting use of other agents aimed at destroying bacteria, namely the surface antibacterials now available in many household products. These too enter the environment. The stage is thus set for an altered microbial ecology, not only in terms of resistant versus susceptible bacteria, but also in terms of the kinds of microorganisms surviving in the treated environment. We currently face multiresistant infectious disease organisms that are difficult and, sometimes, impossible to treat successfully. In order to curb the resistance problem, we must encourage the return of the susceptible commensal flora. They are our best allies in reversing antibiotic resistance.

Animals↗
PubMedDate not supplied

The Wilhelmine E. Key 1999 Invitational lecture. Predicting the evolution of human influenza A.

We studied the evolution of the HA1 domain of the H3 hemagglutinin gene from human influenza virus type A. The phylogeny of these genes showed a single dominant lineage persisting over time. We tested the hypothesis that the progenitors of this single evolutionarily successful lineage were viruses carrying mutations at codons at which prior mutations had helped the virus to avoid human immune surveillance. We found evidence that eighteen hemagglutinin codons appeared to have been under positive selection to change the amino acid they encoded in the past. Retrospective tests show that viral lineages undergoing the greatest number of mutations in the positively selected codons were the progenitors of future H3 lineages in nine of eleven recent influenza seasons. Codons under positive selection were associated with antibody combining sites A or B or the sialic acid receptor binding site. However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.

Codon↗
PubMedDate not supplied

The Wilhelmine E. Key 2001 Invitational Lecture. Estimation of divergence times for a few mammalian and several primate species.

Statistical methods for estimating divergence times by using multiprotein gamma distances are discussed. When a large number of proteins are used, even a small degree of deviation from the molecular clock hypothesis can be detected. In this case, one may use the stem-lineage method for estimating divergence times. However, the estimates obtained by this method are often similar to those obtained by the linearized tree method. Application of these methods to a dataset of 104 proteins from several vertebrate species indicated that the divergence times between humans and mice and between mice and rats are about 96 and 33 million years (MY) ago, respectively. These estimates were obtained by assuming that birds and mammals diverged 310 MY ago. Similarly application of the methods to the protein sequence data from primate species indicated that the human lineage separated from the chimpanzee, gorilla, Old World monkeys, and New World monkeys about 6.0, 7.0, 23.0, and 33.0 MY ago, respectively. In this case the use of two calibration points, that is, the divergence time (13 MY ago) between humans and orangutans and between primates and artiodactyls (90 MY ago) gave essentially the same estimates.

Animals↗
PubMedDate not supplied

The Wilhelmine W. Key 2002 Invitational Lecture. Phylogeography, haplotype trees, and invasive plant species.

The distribution of genetic variants in plant populations is strongly affected both by current patterns of microevolutionary forces, such as gene flow and selection, and by the phylogenetic history of populations and species. Understanding the interplay of shared history and current evolutionary events is particularly confounding in plants due to the reticulating nature of gene exchange between diverging lineages. Certain gene sequences provide historically ordered neutral molecular variation that can be converted to gene genealogies which trace the evolutionary relationships among haplotypes (alleles). Gene genealogies can be used to understand the evolution of specific DNA sequences and relate sequence variation to plant phenotype. For example, in a study of the RPS2 gene in Arabidopsis thaliana, resistant phenotypes clustered in one portion of the gene tree. The field of phylogeography examines the distribution of allele genealogies in an explicit geographical context and, when coupled with a nested clade analysis, can provide insight into historical processes such as range expansion, gene flow, and genetic drift. A phylogeographical approach offers insight into practical issues as well. Here we show how haplotype trees can address the origins of invasive plants, one of the greatest global threats to biodiversity. A study of the geographical diversity of haplotypes in invasive Phragmites populations in the United States indicates that invasiveness is due to the colonization and spread of distinct genotypes from Europe ( Saltonstall 2002). Likewise, a phylogeographical analysis of Tamarix populations indicates that hybridization events between formerly isolated species of Eurasia have produced the most common genotype of the second-worst invasive plant species in the United States.

Biodiversity↗