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Effects of cryopreservation procedures on sperm membranes.

Empirical approaches to semen cryopreservation have resulted in the production of young in a broad range of species. However, acceptable levels of fertility in most domestic animal species has not been achieved. In this review, an attempt has been made to describe the complexity of the sperm plasma membrane and the many steps in a cryopreservation procedure where membrane perturbations can occur. Improvement in sperm cryopreservation procedures will require a careful consideration of the complexity of the sperm plasma membrane, the interaction of its components and the influence of cooling, freezing and thawing on these interactions.

Journal Article↗

Identity status research: implications for career counseling.

The purpose of this paper is to describe an empirical approach to the study of adolescence and to apply research findings to vocational counseling. The study of identity status has enriched and supported Erikson's theory of psychosocial development. Case histories of hypothetical clients in the four identity statuses are presented and different approaches for counseling with such clients are suggested.

Adolescent↗

Short-term testing--are we looking at wrong endpoints?

Short-term testing has been performed and interpreted on the basis of correlation between these tests and animal carcinogenicity. This empirical approach has been the only feasible one, due to a lack of knowledge of the actual genetic endpoints of relevance in carcinogenicity. However, the rapidly growing information on genetic alterations actually involved in carcinogenicity and in particular activation of oncogenes, provides facts of basic importance for the strategy of short-term testing. The presently used sets of short-term tests focus on standard genetic endpoints, mainly point mutations and chromosomal aberrations. Little attention has been paid in that connection to other endpoints, which have been shown or suspected to play an important role in carcinogenicity. These endpoints include gene amplification, transpositions, hypomethylation, polygene mutations and recombinogenic effects. Furthermore, indirect effects, for instance via radical generation and an imbalance of the nucleotide pool, may be of great significance for the carcinogenic and cocarcinogenic effects of many chemicals. Modern genetic and molecular technology has opened entirely new prospects for identifying genetic alterations in tumours and in its turn these prospects should be taken advantage of in order to build up more sophisticated batteries of assays, adapted to the genetic endpoints actually demonstrated to be involved in cancer induction. Development of new assay systems in accordance with the elucidation of genetic alterations in carcinogenicity will probably constitute one of the most important areas in genetic toxicology in the future. From a regulatory point of view the prerequisite for a development in this direction will be a flexibility of the handling of questions concerning short-term testing also at a bureaucratic level.

Animals↗

New perspectives in combined radiotherapy and chemotherapy treatment.

Strategies for developing combined modality treatment for lung cancer have, until now, depended largely on empirical approaches whereby drugs with some activity against advanced disease have been combined with radiation. Survival gains have been modest. The present article emphasizes the need for new approaches that are based on mechanisms of interaction or cooperation between radiation and drugs, such that there is a selective increase in killing of tumour cells. Potential interactions include the use of radiation and drugs to eliminate cell populations which are shown in predictive assays to have differing mechanisms of resistance to the two modalities, selective inhibition of repopulation of tumour cells during radiotherapy by using drugs or biological agents, and selective killing of cells in hypoxic or acidic regions of tumours. The feasibility and potential of such approaches should be evaluated initially in small single-arm studies where outcome in individual patients is related to biological studies of mechanism. Such treatment may need to be individualized (e.g. depending on markers of drug resistance or growth factor receptors). Ultimately, the value of such treatments will need to be evaluated (whether individualized or generic) against standard treatment in large randomized trials. Guidelines for the conduct of such trials are indicated with emphasis on quality of life, assessment of costs and benefits, and involvement of patients in clinical decision making.

Animals↗

Modelling episodic acidification of surface waters: the state of science.

Field studies of chemical changes in surface waters associated with rainfall and snowmelt events have provided evidence of episodic acidification of lakes and streams in Europe and North America. Modelling these chemical changes is particularly challenging because of the variability associated with hydrological transport and chemical transformation processes in catchments. This paper provides a review of mathematical models that have been applied to the problem of episodic acidification. Several empirical approaches, including regression models, mixing models and time series models, support a strong hydrological interpretation of episodic acidification. Regional application of several models has suggested that acidic episodes (in which the acid neutralizing capacity becomes negative) are relatively common in surface waters in several regions of the US that receive acid deposition. Results from physically based models have suggested a lack of understanding of hydrological flowpaths, hydraulic residence times and biogeochemical reactions, particularly those involving aluminum. The ability to better predict episodic chemical responses of surface waters is thus dependent upon elucidation of these and other physical and chemical processes.

Journal Article↗

Innovation, ideology and innocence.

Innovative solutions are required to deal with the inadequacies of existing medical education programmes, in both the developed and developing countries, if we are to promote the evolution of more acceptable, more efficient and more effective health care. The newly formed Network of Community-oriented Educational Institutions for Health Sciences is attempting to promote a series of educational and organisational innovations, aimed at the preparation of health professionals who will be better equipped and better motivated to meet the real health needs of the populations they are to serve. Such innovations encounter many obstacles, of which ideologically-based inflexibility of thought is the most important. Ideologies are here defined, in Barnett's words, as "patterns of belief ... quasi-conceptual, quasi-affective sets assumed to be true", having the power to prohibit "rigorous or experimental examination of novel experience." Such systems of thought have 'negative, restrictive and pathological effects' on the development of innovative solutions to complex problems. A particularly destructive and inhibiting stereotype has flowed from an ideological commitment to the achievement of 'international excellence'. A state of what in this paper is called 'innocence' is regarded as mandatory for the implementation of studies based on a commitment to the empirical approach, to the null hypothesis and above all to the evaluation of the process and outcome of educational and other interventions in the health care system.

Communication↗

Allocating medical resources in rural America: alternative perceptions of justice.

In national debates concerning the allocation of medical resources rural America is a neglected topic, and the voices of rural health professionals are seldom heard. This paper highlights the special problems encountered in allocating medical resources within the rural setting and indicates the strategies that rural residents compose for dealing with them. Our findings are based on a study consisting of in-depth open-ended interviews with family physicians in the rural northwest United States. We contrast the approach to justice expressed by these rural physicians with the conception of justice that dominates Western philosophy and bioethics. In the course of our discussion, the diversity within Western culture becomes apparent. We discuss strategies for incorporating different perspectives into local and national allocation debates, clarify the reasons why a more encompassing approach to justice is necessary, and review the implications of our work for future research.

Beneficence↗

Ethical and legal implications of the new genetics: issues for discussion.

The so-called 'new genetics,' a phrase sometimes associated with The Human Genome Initiative, poses no really new ethical problems, but exacerbates old ones. The issues of most concern to geneticists and their patients are summarized under the eleven headings below. These issues emerged from a 19-nation study of ethics and genetics in 1985-86 and from preliminary work on a forthcoming 36-nation study by the same authors.

Abortion, Legal↗

Hot and cold in transformation: is Iban medicine humoral?

Iban categories of hot and cold are examined in the context of humoral medical systems in southeast Asia. These categories are more than binary and oppositional: they are also contradictory and can only be understood in terms of their capacity for transformation in 'depth'. Analysis of the Iban epistemology of temperature sensation reveals the limitations of reductionist empirical approaches to hot and cold. Illness is apprehended, at one level, in terms of unusual conjunctions of opposite temperatures which signify a deeper disturbance in the relationship between body and soul, humans and spirits. Iban therapy redefines and relocates these categories in their proper place and at their appropriate level. It progresses from hot lay treatments to cool ritual treatments, yet cannot be accounted for within a limited framework of homeostatic balance. This paper develops an ethnographically grounded definition of humoralism which emphasizes non-reductive logic, cultural practice and transformation. The key element, transformation, is defined as a transition between categories and a shift in the level of interpretation which fundamentally alter the Iban experience of body and illness.

Borneo↗

Solubilization of phospholipids by detergents. Structural and kinetic aspects.

Most amphiphiles in biological membranes including phospholipids, steroids, and membrane proteins are insoluble amphiphiles and would form liquid crystals or insoluble precipitates alone in aqueous media. Detergents are soluble amphiphiles and above a critical concentration and temperature form micelles of various sizes and shapes. Much of the recent progress in studying the insoluble amphiphiles is due to the formation of thermodynamically stable isotropic solutions of these compounds in the presence of detergents. This process, which is commonly denoted as "solubilization,' involves transformation of lamellar structures into mixed micelles. The information available to date on the solubilization of phospholipids, which constitute the lipid skeleton of biomembranes, by the common detergents is discussed in this review, both with respect to the kinetics of this process and the structure of the various phospholipid-detergent mixed micelles formed. It is hoped that this discussion will lead to somewhat more useful, although still necessarily fairly empirical, approaches to the solubilization of phospholipids by detergents.

Animals↗

Non-genotoxic factors in the carcinogenetic process: problems of detection and hazard evaluation.

In the classical two-stage models of carcinogenesis, initiation has been usually related to a DNA-damage/gene-mutation event, while promotion has been related to the non-genotoxic effects of clonal expansion of preneoplastic cells and/or modulation of cell differentiation. It is now clear that the process of carcinogenesis is linked to more than one irreversible alteration in the genome. Likewise, we can envisage that non-genotoxic events can take place after perhaps 0, 1, 2 or more irreversible alterations in the genome. Initiating and promoting activities of a chemical can be considered clearly separated in theory, but in practice, the chemicals we work with only rarely will be purely of the genotoxic or non-genotoxic type. We will discuss an empirical approach to classify genotoxic or prevalently non-genotoxic chemical carcinogens. For prevalently non-genotoxic carcinogens we will analyze what fraction of them can be detected as promoters of in vivo rat liver carcinogenesis. We will analyze carcinogenic potency of genotoxic and non-genotoxic carcinogens.

Animals↗

Simulation of fractograms of fat emulsions in power-programmed sedimentation field-flow fractionation (SdFFF).

A quasi-empirical approach to the simulation of fractograms was examined to verify that the elution behavior of emulsions in power-based field programmed sedimentation field-flow fractionation (SdFFF) is consistent and predictable. The approach was applied to Intralipid, a commercial soybean emulsion and to an investigational medium chain triglyceride emulsion. The simulations predicted the fractograms that were obtained under various conditions of field strength, field decay and velocity of the suspending fluid, using distribution parameters obtained from one preliminary measurement of size distribution profile. Predicted fractograms were compared to experimental ones, under various fractionating powers. Good agreement was observed in most cases, in which interference of the secondary relaxation effects was not effective. The agreement confirmed the applicability of the approach to emulsions and that the simulations can be used instead of actual experiments for the optimization of their characterization by power-programmed SdFFF.

Chemical Fractionation↗

Dosimetry considerations when treating inclined lesions.

The planning and subsequent treatment of inclined lesions is difficult when non-vertical or non-horizontal beams are to be employed. Rotations of the patient support assembly and the collimator further complicate the planning. The present work describes an empirical approach that is relatively simple (requires protractor and calculator). Frequently, plans must be generated in planes other then the central axis and a caution about the location of the "SAD" point will be discussed.

Humans↗

Using saccade tasks as a tool to analyze executive dysfunctions in schizophrenia.

Executive dysfunctions can be frequently observed in schizophrenia. They are more persistent than psychotic symptoms and are assumed to contribute to a variety of clinical signs of the disease. However, the cognitive mechanisms underlying dysexecutive behaviors are not yet understood. The aim of this article is to demonstrate how saccade tasks can be used to analyze the mechanisms involved in the dysexecutive syndrome of schizophrenic patients. There are numerous reports showing that schizophrenic patients make many unwanted reflexive saccades in the antisaccade task. These errors are usually explained by an impairment of a distinct inhibitory mechanism. However, unwanted reflexive saccades may also be secondary to a more fundamental deficit in activating goal-directed behavior. Recent theoretical and empirical approaches to this issue are reviewed and discussed. An integrative view of deficits in inhibition, goal-directed behavior, and working memory in schizophrenic patients is proposed.

Fixation, Ocular↗

Circular dichroism studies of subtilisin Carlsberg immobilised on micron sized silica particles.

Immobilised enzymes are widely used in industry, but the reasons for loss of activity of such biocatalysts are usually not known. We have used circular dichroism (CD) to investigate the structure of one such system, i.e., subtilisin Carlsberg (SC) immobilised on silica gel particles (60 microm). A number of technical problems have to be overcome in order to obtain appropriate data from which conclusions can be drawn. A rotating cell holder has been developed to avoid sedimentation of the silica particles during the collection of spectra. By moving the cell holder as close as possible to the detector window, the effects of differential scattering can be minimised. However, the effects of absorption flattening limit the extent to which reliable quantitative information on secondary structure content can be obtained from far UV CD studies. We have used an empirical approach based on absorbance units derived from the high-tension voltage to correct for absorption flattening effects. After applying the correction there was satisfactory agreement with the solution spectra. Comparison of the fresh and used (inactive) SC-silica gel spectra in organic media reveals substantial change in the secondary structure. Additional evidence for loss of native conformation is provided by the significant decrease in the near UV CD spectrum. These results for the first time clearly demonstrate the origin of enzyme instability in the immobilised state.

Bacillus↗

Determination of helical membrane protein topology using residual dipolar couplings and exhaustive search algorithm: application to phospholamban.

Dipolar waves are distinct hallmarks of both the secondary and tertiary structures of alpha-helical proteins that are immobilized in membrane bilayers or embedded in anisotropic media. We present a simple, semi-empirical approach that exploits the modulation of the amplitude and average of dipolar waves to determine the topology of alpha-helical proteins. Moreover, we describe the application of this method for the structural determination of a detergent solubilized membrane protein, phospholamban (PLB) that is involved in calcium regulation of cardiac muscle. When combined with high-resolution solid-state NMR data, this method can serve as a fast route for determining the topology of helical membrane proteins solubilized in detergent micelles.

Algorithms↗

Alcohol abuse and suicide attempts among youth.

This study uses the Youth Risk Behavior Survey (YRBS) and the National Comorbidity Survey (NCS) to explore the causal relationship between alcohol abuse (binge drinking and clinically defined alcohol use disorders) and suicide attempts among youth. We use an empirical approach that allows one to assess the possible existence and strength of a causal relationship without relying on identifying assumptions. Our results suggest that a causal relationship between binge drinking and suicide attempts is very unlikely. The findings, however, support a causal relationship between clinically defined alcohol use disorders and suicide attempts among girls.

Adolescent↗

BCG dose reduction by decreasing the instillation frequency: effects on local Th1/Th2 cytokine responses in a mouse model.

OBJECTIVES: Based on the requirement of a Th1 immune response for clinical efficacy, and incited by the arbitrary induction scheme, frequent side effects and the empirical approach in improving BCG immunotherapy for superficial bladder cancer, an alternative intravesical BCG treatment schedule for dose reduction was investigated without compromising Th1 cytokine induction in the bladder in a mouse model. METHODS: Mice were submitted to 6 weekly BCG instillations and treatment schedules omitting intermediate instillations during this standard scheme. Th1 (IFN-gamma, IL-2, IL-12p40), and Th2 (IL-10, IL-4) cytokine responses in individual mouse bladders were measured by a semiquantitative RT-PCR based method. RESULTS: A schedule of only two BCG instillations, administered in week 1 and week 6, resulted in induction of at least the same levels of IFN-gamma, IL-2 and IL-12p40 Th1 cytokine mRNA compared to 6 weekly instillations, whereas significantly lower levels of Th2 cytokines IL-10 and IL-4 mRNA were observed. CONCLUSIONS: During the 6-week period the intermediate weekly BCG instillations 2, 3, 4, and 5 do not contribute to Th1 cytokine upregulation in the bladder, provided that the BCG dose is sufficient. Whether such a reduced BCG frequency schedule has immune stimulating capacity and therapeutic efficacy associated with less side effects in patients remains to be investigated.

Administration, Intravesical↗