In vivo gene expression: DNA electrotransfer

The use of electric pulses to deliver therapeutic molecules to tissues and organs in vivo is a rapidly growing field of research. Electrotransfer can be used to deliver a wide range of potentially therapeutic agents, including drugs, proteins, oligonucleotides, RNA and DNA. Optimization of this approach depends upon a number of parameters such as target organ accessibility, cell turnover, microelectrode design, electric pulsing protocols and the physiological response to the therapeutic agent. Many organs have been successfully transfected by electroporation, including skin, liver, skeletal and cardiac muscle, male and female germ cells, artery, gut, kidney, retinal ganglion cells, cornea, spinal cord, joint synovium and brain. Electrotransfer technology is relevant in a variety of research and clinical settings including cancer therapy, modulation of pathogenic immune reactions, delivery of therapeutic proteins and drugs, and the identification of drug targets by the modulation of normal gene expression. This, together with the capacity to deliver very large DNA constructs, greatly expands the research and clinical applications of in vivo DNA electrotransfer.

A way forward for land-use planning to achieve policy goals by using spatial modelling scenarios

This paper investigates how demographic (socioeconomic) and land-use (physical and environmental) data can be integrated within a decision support framework to formulate and evaluate land-use planning scenarios. A case-study approach is undertaken with land-use planning scenarios for a rapidly growing coastal area in Australia, the Shire of Hervey Bay. The town and surrounding area require careful planning of the future urban growth between competing land uses. Three potential urban growth scenarios are put forth to address this issue. Scenario A ('continued growth') is based on existing socioeconomic trends. Scenario B ('maximising rates base') is derived using optimisation modelling of land-valuation data. Scenario C ('sustainable development') is derived using a number of social, economic, and environmental factors and assigning weightings of importance to each factor using a multiple criteria analysis approach. The land-use planning scenarios are presented through the use of maps and tables within a geographical information system, which delineate future possible land-use allocations up until 2021. The planning scenarios are evaluated by using a goal-achievement matrix approach. The matrix is constructed with a number of criteria derived from key policy objectives outlined in the regional growth management framework and town planning schemes. The authors of this paper examine the final efficiency scores calculated for each of the three planning scenarios and discuss the advantages and disadvantages of the three land-use modelling approaches used to formulate the final scenarios.

Molecular structure and function of the glycine receptor chloride channel

The glycine receptor chloride channel (GlyR) is a member of the nicotinic acetylcholine receptor family of ligand-gated ion channels. Functional receptors of this family comprise five subunits and are important targets for neuroactive drugs. The GlyR is best known for mediating inhibitory neurotransmission in the spinal cord and brain stem, although recent evidence suggests it may also have other physiological roles, including excitatory neurotransmission in embryonic neurons. To date, four alpha-subunits (alpha1 to alpha4) and one beta-subunit have been identified. The differential expression of subunits underlies a diversity in GlyR pharmacology. A developmental switch from alpha2 to alpha1beta is completed by around postnatal day 20 in the rat. The beta-subunit is responsible for anchoring GlyRs to the subsynaptic cytoskeleton via the cytoplasmic protein gephyrin. The last few years have seen a surge in interest in these receptors. Consequently, a wealth of information has recently emerged concerning Glyl? molecular structure and function. Most of the information has been obtained from homomeric alpha1 GlyRs, with the roles of the other subunits receiving relatively little attention. Heritable mutations to human GlyR genes give rise to a rare neurological disorder, hyperekplexia (or startle disease). Similar syndromes also occur in other species. A rapidly growing list of compounds has been shown to exert potent modulatory effects on this receptor. Since GlyRs are involved in motor reflex circuits of the spinal cord and provide inhibitory synapses onto pain sensory neurons, these agents may provide lead compounds for the development of muscle relaxant and peripheral analgesic drugs.

Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modem toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

The epidemiology of dysphagia: Describing the problem - are we too late?

The assessment and management of dysphagia is a rapidly growing part of speech pathology clinical practice for both adult and paediatric populations, yet there is limited information available regarding the epidemiology of dysphagia. Very few studies have defined the characteristics of the disorder, its incidence/prevalence in various populations, the natural history of the disorder or the relative risks, comorbidities and outcomes associated with dysphagia. The current paper will identify some fundamental questions that as yet remain unanswered and highlight areas of future research that are required in order for us to have a better understanding of dysphagia and inform assessment and management. In conclusion, the authors propose an epidemiological framework and highlight information needs in the field of dysphagia. This framework urges future dysphagia research to be informed and underpinned by sound epidemiological principles.

Sample registration of vital events with verbal autopsy: a renewed commitment to measuring and monitoring vital statistics

Registration of births, recording deaths by age, sex and cause, and calculating mortality levels and differentials are fundamental to evidence-based health policy, monitoring and evaluation. Yet few of the countries with the greatest need for these data have functioning systems to produce them despite legislation providing for the establishment and maintenance of vital registration. Sample vital registration (SVR), when applied in conjunction with validated verbal autopsy, procedures and implemented in a nationally representative sample of population clusters represents an affordable, cost-effective, and sustainable short- and medium-term solution to this problem. SVR complements other information sources by producing age-, sex-, and cause-specific mortality data that are more complete and continuous than those currently available. The tools and methods employed in an SVR system, however, are imperfect and require rigorous validation and continuous quality assurance; sampling strategies for SVR are also still evolving. Nonetheless, interest in establishing SVR is rapidly growing in Africa and Asia. Better systems for reporting and recording data on vital events will be sustainable only if developed hand-in-hand with existing health information strategies at the national and district levels; governance structures; and agendas for social research and development monitoring. If the global community wishes to have mortality measurements 5 or 10 years hence, the foundation stones of SVR must be laid today.

Research in leadership, self, and identity: A sample of the present and a glimpse of the future

Researchers in leadership effectiveness are paying increasing attention to the role of follower self-concept and identity as a mediator and moderator of the effectiveness of leadership. In this introductory article, we provide a short outline of this rapidly growing field of research, briefly introduce the articles presented in this special issue on leadership, self, and identity, and highlight key themes for future research that we feel emerge from these studies. These themes include greater attention to the dynamic interplay between leaders and followers, the incorporation of theories of fairness, and the role of leader self-concept. (c) 2005 Elsevier Inc. All rights reserved.

International Union of Pharmacology. LXVI. Orphan nuclear receptors

Half of the members of the nuclear receptors superfamily are so-called orphan receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.