Marital therapy for the elderly.

Little attention has been paid to marital therapy for the elderly in spite of its relevance to morale and emotional problems. Physical illness is of particular significance in altering the dynamics of the marital relationship. Retirement and financial problems, as well as changes in sexual activity and gender roles, are also important. However, radical changes in patterns of behaviour cannot be expected. Therapeutic techniques must be altered for this age group, and the therapist must be active, giving and concretely helpful. As with therapy for younger couples, children may need to be involved in the therapy sessions. Family physicians should be a main source of help for marital problems among the elderly. However, because problems related to countertransference must be faced, working with the elderly will not be for everyone.     

The hospital component of vocational training for general practice.

Trainees and educationalists in general practice have some grounds for suggesting that the hospital component of vocational training should be restructured and teaching improved. However, the implications for other trainees and secondary care have to be considered. Changes that are needed include a curriculum for senior house officers in each specialty; appointment of training consultants with the necessary skills; and a different attitude by everyone towards study leave, including arrangements for funding. The optimum duration of hospital posts for trainees in general practice might be shorter than now, but the effects on others must be considered and competencies guaranteed in a briefer training period. Changes in the regulations for vocational training could help to improve specialist experience if trainees in general practice were allowed to be supernumerary. Alternatively, senior house officer posts for trainees in general practice could be split between secondary and primary care, thus encouraging a broader perspective.     

Assessment of the potential germ cell mutagenicity of industrial and plant protection chemicals as part of an integrated study of genotoxicity in vitro and in vivo

An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.     

Interferon induction and utilization

The interferon mechanism offers the hope for moderate to high level prophylactic immunity of broad antiviral spectrum but of relatively short duration. Economic and biological considerations offer little hope for utilization of exogenous interferon as a prophylactic or therapeutic substance, unless but a small part of the total molecule be found to carry the activity. The real promise for interferon application is in the administration of suitable inducers so as to cause the body to produce and distribute its own interferon. Certain ribonucleic acids (RNA's) offer hope for high level potency as inducers without adverse effect. The condition for interferon induction by ribonucleic acids appears to be double- or multistrandedness and freedom from inhibitors. These can be of biologic or synthetic origin. The mechanism of action of interferon is not fully understood but appears to fit into the Jacob-Monod model involving two phases: first, a derepression by the inducer to cause the cell to form interferon and second, a derepression by interferon to cause recipient cells to form the active substance which acts by preventing translation from viral messenger RNA. Double or multistranded RNA of viral or other origin appears to be unique to the cell and serves as the alert to it to produce interferon in phase 1. Greatest need for interferon is clearly for those diseases in which there is a multiplicity of immunologic types in excess of the numbers which could be put into a vaccine as, e.g., the common cold and enteric viruses. There might be some overall therapeutic benefit also if inducer were given early enough in infection. Special value for interferon induction might derive by administration in early life before the development of immunologic maturity, as a means for preventing infection with oncogenic or other viruses. Additionally, suitable inducers might be capable of interrupting the reinfection cycle in virus-dependent malignancies. The favorable outlook for interferon utilization must always be tempered with the realization that under certain as yet undiscovered situations, adverse rather than beneficial effects might result from indution of interferon. It is not impossible that in certain special circumstances, as in ordinary immunologic responses, it might be more beneficial to negate rather than to promote the effect.     

CURRENT NOTES AND NOTICES

These are collated by Gwen Bonham, the Union's Administrative Secretary. Requests for the publication of information or other required assistance will be sympathetically considered. Publicity will gladly be given to relevant grants and awards that can be applied for, and to new societies which might be of interest to our readers. Details of conferences and meetings will also be included if sent to the Administrative Secretary at least 6 months in advance of the event. All items for Current Notes and Notices should be sent to the BOU, % The Natural History Museum, Tring, Hertfordshire HP23 6AP, UK .     

Towards reliable spike-train recordings from thousands of neurons with multielectrodes

The new generation of silicon-based multielectrodes comprising hundreds or more electrode contacts offers unprecedented possibilities for simultaneous recordings of spike trains from thousands of neurons. Such data will not only be invaluable for finding out how neural networks in the brain work, but will likely be important also for neural prosthesis applications. This opportunity can only be realized if efficient, accurate and validated methods for automatic spike sorting are provided. In this review we describe some of the challenges that must be met to achieve this goal, and in particular argue for the critical need of realistic model data to be used as ground truth in the validation of spike-sorting algorithms.     

Principles and strategies in breeding for higher salt tolerance

Summary Salinity is an environmental component that usually reduces yield. Recent advances in the understanding of salt effects on plants have not revealed a reliable physiological or biochemical marker that can be used to rapidly screen for salt tolerance. The necessity of measuring salt tolerance based upon growth in saline relative to non-saline environments makes salt tolerance measurements and selection for tolerance difficult. Additionally, high variability in soil salinity and environmental interactions makes it questionable whether breeding should be conducted for tolerance or for high yield. Genetic techniques can be used to identify the components of variation attributable to genotype and environment, and the extent of genetic variation in saline and nonsaline environments can be used to estimate the potential for improving salt tolerance. Absolute salt tolerance can be improved best by increasing both absolute yield and relative salt tolerance.     

Ethical and regulatory issues arising from proteomic research and technology

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.     

Performance modeling and simulation of biochemical process sequences with interacting unit operations

Many biochemical processes consist of a sequence of operations for which optimal operating conditions (setpoints) have to be determined. If such optimization is performed for each operation separately with respect to objectives defined for each operation individually, overall process performance is likely to be suboptimal. Interactions between unit operations have to be considered, and a unique objective has to be defined for the whole process. This paper shows how a suitable optimization problem can be formulated and solved to obtain the best overall set of operating conditions for a process. A typical enzyme production process has been chosen as an example. In order to arrive at a demonstrative model for the entire sequence of unit operations, it is shown how interaction effects may be accommodated in the models. Optimal operating conditions are then determined subject to a global process objective and are shown to be different from those resulting from optimization of each separate operation. As this strategy may result in an economic benefit, it merits further research into interaction modeling and performance optimization.     

Safety and economic aspects of continuous mammalian cell culture.

Mammalian cell cultures are the most appropriate host cells for recombinant DNA derived products if complex protein structures have to be synthesized in their native form. Due to their physiological behaviour they grow either adherent or in suspension. For the attachment of adherent cells, microcarriers or wire springs can be applied to increase the internal surface of the bioreactor. Both systems provide a simplified media exchange but, however, show some limitations in scale up. In contrast, suspension culture systems as homogeneous systems independent of any carrier have not shown any limitation in scale up. Because most cell lines which are of commercial interest grow in suspension, this technology is best advanced and used in batch and continuous mode. Although mammalian cell cultures are sensitive to hydrodynamic shear forces, technologies for deep tank production are developed which allow stirrer tip speed of up to 1.5 m s-1 sufficient for oxygen uptake, suspension of cells and homogeneous supply with nutrients. For long term bioprocesses without selection pressure it has to be considered that transformed cell lines might show genetic instability due to their variations of chromosomes. In addition, sterile technology becomes an important factor in long term bioprocesses. The decision as to which cell culture system should be chosen, whether batch or continuous processes should be applied essentially is based on the capital investment, the amount of material to be produced, genetic stability of the production cell line, reliability of sterile technology and the flexibility required in the production plant. Under the assumption that 20 kg of a protein have to be produced per year and the same product concentrations in the harvest fluid are reached in the batch process and for instance in the chemostat, it can be considered that the capital investment for one 10,000 l batch process and a 2 x 2,000 l continuous process, necessary to produce the amount of material, is comparable. Risk of microbial contamination or technical failure can be considered to be fairly low in the batch process. The economic risk for long term bioprocess in the chemostat can be expected to be medium and high in the perfusion system which is in the large scale not technically fully satisfactory. In addition, due to the longer down time period after contaminations and the start up of the continuous process, the annual yield of the batch process can be considered to be higher.(ABSTRACT TRUNCATED AT 400 WORDS)     

Genetic improvement of willow for bioenergy and biofuels

Willows (Salix spp.) are a very diverse group of catkin-bearing trees and shrubs that are widely distributed across temperate regions of the globe. Some species respond well to being grown in short rotation coppice (SRC) cycles, which are much shorter than conventional forestry. Coppicing reinvigorates growth and the biomass rapidly accumulated can be used as a source of renewable carbon for bioenergy and biofuels. As SRC willows re-distribute nutrients during the perennial cycle they require only minimal nitrogen fertilizer for growth. This results in fuel chains with potentially high greenhouse gas reductions. To exploit their potential for renewable energy, willows need to be kept free of pests and diseases and yields need to be improved without significantly increasing the requirements for fertilizers and water. The biomass composition needs to be optimized for different end-uses. Yields also need to be sustainable on land less productive for food crops to reduce conflicts over land use. Advances in understanding the physiology and growth of willow, and in the identification of genes underlying key traits, are now at the stage where they can start to be used in breeding programs to help achieve these goals.     

Is there chaos in the brain? I. Concepts of nonlinear dynamics and methods of investigation

In the light of results obtained during the last two decades in a number of laboratories, it appears that some of the tools of nonlinear dynamics, first developed and improved for the physical sciences and engineering, are well-suited for studies of biological phenomena. In particular it has become clear that the different regimes of activities undergone by nerve cells, neural assemblies and behavioural patterns, the linkage between them, and their modifications over time, cannot be fully understood in the context of even integrative physiology, without using these new techniques. This report, which is the first of two related papers, is aimed at introducing the non expert to the fundamental aspects of nonlinear dynamics, the most spectacular aspect of which is chaos theory. After a general history and definition of chaos the principles of analysis of time series in phase space and the general properties of chaotic trajectories will be described as will be the classical measures which allow a process to be classified as chaotic in ideal systems and models. We will then proceed to show how these methods need to be adapted for handling experimental time series; the dangers and pitfalls faced when dealing with non stationary and often noisy data will be stressed, and specific criteria for suspecting determinism in neuronal cells and/or assemblies will be described. We will finally address two fundamental questions, namely i) whether and how can one distinguish, deterministic patterns from stochastic ones, and, ii) what is the advantage of chaos over randomness: we will explain why and how the former can be controlled whereas, notoriously, the latter cannot be tamed. In the second paper of the series, results obtained at the level of single cells and their membrane conductances in real neuronal networks and in the study of higher brain functions, will be critically reviewed. It will be shown that the tools of nonlinear dynamics can be irreplaceable for revealing hidden mechanisms subserving, for example, neuronal synchronization and periodic oscillations. The benefits for the brain of adopting chaotic regimes with their wide range of potential behaviours and their aptitude to quickly react to changing conditions will also be considered.     

Review: Assessment of dairy cow welfare at pasture: measures available,gaps to address,and pathways to development of ad-hoc protocols

Pasture is generally perceived as positive for dairy cow welfare, but it nevertheless exposes cows to heat, parasites, and other challenges. This review is intended for people ready to design comprehensive protocols for assessing the welfare of dairy cows at pasture. We provide an overview of the benefits and risks of pasture for cows, and then go on to identify the available and feasible measures for assessing cow welfare at pasture and the gaps that need to be addressed to develop specific welfare measures. Some of the measures from on-farm welfare assessment protocols designed for indoor use (e.g. Welfare Quality®) are relevant for cows at pasture (e.g. lameness scoring). However, the timing, location and/or method for certain measures (e.g. observation of social behaviour) need to be adapted to the pasture context, as cows at pasture can roam over a large area. Measures to address specific pasture-related risks (e.g. heat stress, biosecurity) or benefits (e.g. expression of a wide range of behaviours) should be implemented in order to capture all dimensions of cow welfare at pasture. Furthermore, cow welfare is liable to vary over the grazing season due to changes in weather conditions, grass quality and pasture plots that induce variations in lying surface conditions, food availability, distance to walk to the milking parlour, and so on. It is therefore important to investigate the variability in different welfare measures across the pasture season to check whether they hold stable over time and, if not, to determine solutions that can give an overview across the grazing season. Sensors offer a promising complement to animal and environment observations, as they can capture long-term animal monitoring data, which is simply not possible for a one-day welfare-check visit. We conclude that some measures validated for indoor situations can already be used in pasture-based systems, while others need to be validated for their fitness for purpose and/or use in pasture conditions. Furthermore, thresholds should probably be determined for measures to fit with pasture contexts. If all measures can be made adaptable to all situations encountered on farms or variants of the measures can at least be proposed for each criterion, then it should be possible to produce a comprehensive welfare assessment protocol suitable for large-scale use in near future.     

Evaluation of the Biological Activity of Several Analogs of the Dopaminergic Neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine

Several analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and screened for their capacity to be oxidized by monoamine oxidase (MAO-A or MAO-B) and their capacity to produce nigrostriatal dopaminergic neurotoxicity in mice. All of the compounds were relatively weak substrates for MAO-A but many of the compounds were found to be good substrates for MAO-B. Only three of the compounds, in addition to MPTP itself, were found to be neurotoxic. These were 1-methyl-4-cyclohexyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine and 1-methyl-4-(3'-methoxyphenyl)-1,2,3,6-tetrahydropyridine. All three of these neurotoxic compounds were found to be substrates for MAO-B; in contrast no compound was found to be neurotoxic that was not oxidized by MAO-B. The capacity of the compounds studied to be oxidized by MAO-B appears to be an important aspect of the neurotoxic process.     

Sample size determination

Scientists who use animals in research must justify the number of animals to be used, and committees that review proposals to use animals in research must review this justification to ensure the appropriateness of the number of animals to be used. This article discusses when the number of animals to be used can best be estimated from previous experience and when a simple power and sample size calculation should be performed. Even complicated experimental designs requiring sophisticated statistical models for analysis can usually be simplified to a single key or critical question so that simple formulae can be used to estimate the required sample size. Approaches to sample size estimation for various types of hypotheses are described, and equations are provided in the Appendix. Several web sites are cited for more information and for performing actual calculations     

The chemoinvasion assay: a method to assess tumor and endothelial cell invasion and its modulation

Invasive and metastatic cells, as well as endothelial cells, must cross basement membranes (BMs) in order to disseminate or to form new blood vessels. The chemoinvasion assay using the reconstituted BM Matrigel in Boyden blind-well chambers is a very rapid, easy, inexpensive and flexible test that can be used to quantify the invasive potential of most cell types; it can be applied to detect the migratory activity associated with matrix degradation and can also be adapted to study the selective degrading activity on different matrix substrates. Transwell inserts can also be used. Once the optimal experimental conditions are empirically determined for specific cellular models, the chemoinvasion assay can be used for the screening of inhibitors of invasiveness and angiogenesis, or to select for invasive cellular populations. This protocol can be completed in 9 h.     

The use of biomarkers in surveillance, medical screening, and intervention

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.     

Human DNA polymorphisms and methods of analysis.

The current predominant method of analyzing base substitution polymorphisms, RFLP analysis, is likely to be gradually supplanted by methods based on PCR because of the improved sensitivity and genotyping rate. The most promising PCR methods for analysis appear to be allele-specific PCR and single-stranded conformational analysis. The single-stranded conformation approach has already been applied to the scanning of cystic fibrosis exons for new mutations. Linkage mapping projects that cover large segments of the human genome will probably rely, in the coming years, primarily on tandem repeat polymorphisms, particularly microsatellite polymorphisms. Microsatellite polymorphisms have at least a fourfold advantage over base substitution RFLPs because they are twice as informative and can be typed at at least twice the rate. The facioscapulohumeral muscular dystrophy gene was recently mapped in just 6 weeks using microsatellite polymorphisms. Because of the informativeness handicap, it will be difficult for base substitution polymorphisms to overtake tandem repeat markers for large-scale linkage mapping. Methods that allow base substitution polymorphisms to be typed at two or three times the rate of microsatellite markers would have to be developed. Most of the other applications of DNA polymorphisms described in the introduction are also increasingly likely to rely on highly informative tandem repeat markers in the future. Methods for analysis will probably be based on PCR. It is easy to envisage, for example, an automated method for large-scale DNA fingerprinting of individuals based upon a standard set of highly informative, dependable microsatellite polymorphisms. Methods for analyzing base substitution polymorphisms will continue to be important for the diagnostic detection of disease-gene alleles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drought as a challenge for the plant breeder

Since agriculture began, drought has been on of the major plagues affecting crop production causing famine and death. Despite many decades of research, drought continues to be a major challenge to agricultural scientists. This is due to the unpredictability of its occurrence, severity, timing and duration; and to the interaction of drought with other abiotic stresses, particularly extremes of temperature and variations in nutrients availability; and with biotic stresses. Breeding has not been as effective in improving crop production under drought-stress conditions as it has in their absence — or where the stress can be alleviated by irrigation. This paper argues that the relative lack of success of breeding for stress conditions in general, and for drought-stress conditions in particular, can be partly attributed to use of the same breeding approach that is successful for favourable environments. A different breeding approach for drought-stress conditions is discussed in relation to the environment in which selection should be conducted, the germplasm to be used, and the experimental designs and plot techniques to be employed.     

Insect-truffle interactions – potential threats to emerging industries?

Truffle harvests are declining in Europe, due to droughts, and this offers an opportunity for production to be developed in countries such as the UK and Poland, where rainfall tends to be higher. Drier Mediterranean summers seem to be associated with a decrease in the harvest of the Périgord truffle (Tuber melanosporum) in Spain, France and Italy. However, other species, for example the Burgundy truffle (Tuber aestivum) offer opportunities for production in the more temperate environments north of the Alps. Truffles across Europe can be infested by insect larvae, seriously reducing their economic and culinary quality. Here, using a combination of literature sources and a field survey, we present a commentary on insects attacking truffles, aiming to highlight those species that could be potential pests in the British and Polish emergent industries. There is a remarkable disparity in coincidence of records of insects and truffles in these countries, yet a survey in Poland confirms that insects can be abundant. We discuss reasons for this disparity and suggest that biochemical methods could easily be developed for detection of the truffles and their attackers.