Access to adult liver transplantation in Canada: a survey and ethical analysis.

OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and because the primary limiting factor is organ supply, increased organ acquisition efforts are needed.     

Therapies cognitives des dysfonctions sexuelles

The basis of cognitive therapy is an analysis of the way an individual thinks and perceives in order to analyse what will affect his feelings and behavior. The patterns of thoughts will determine in which way the ideas will be perceived and conceived. The author provides a list and, taking erectile dysfunction as a model, gives examples of dysfunctional schemas. Thus the essential points of the treatment are better known. This type is particularly interesting as it corresponds to the way the majority of patients think, and who can tackle it very easily. In our experience, 60% of patients choose a cognitive-behavioral therapy when offered a list of possible treatments for their dysfunction. This should be complementary to any therapy, even technical.     

AGRA: analysis of gene ranking algorithms

Often, the most informative genes have to be selected from different gene sets and several computer gene ranking algorithms have been developed to cope with the problem. To help researchers decide which algorithm to use, we developed the analysis of gene ranking algorithms (AGRA) system that offers a novel technique for comparing ranked lists of genes. The most important feature of AGRA is that no previous knowledge of gene ranking algorithms is needed for their comparison. Using the text mining system finding-associated concepts with text analysis. AGRA defines what we call biomedical concept space (BCS) for each gene list and offers a comparison of the gene lists in six different BCS categories. The uploaded gene lists can be compared using two different methods. In the first method, the overlap between each pair of two gene lists of BCSs is calculated. The second method offers a text field where a specific biomedical concept can be entered. AGRA searches for this concept in each gene lists' BCS, highlights the rank of the concept and offers a visual representation of concepts ranked above and below it. AVAILABILITY AND IMPLEMENTATION: Available at http://agra.fzv.uni-mb.si/, implemented in Java and running on the Glassfish server. CONTACT: simon.kocbek@uni-mb.si.     

The DrugPattern tool for drug set enrichment analysis and its prediction for beneficial effects of oxLDL on type 2 diabetes

Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bioinformatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules of a list of drugs are limited. In this study, we developed a web-based tool, DrugPattern, for drug set enrichment analysis. We first collected and curated 7019 drug sets, including indications, adverse reactions, targets, pathways, etc. from public databases. For a list of interested drugs, DrugPattern then evaluates the significance of the enrichment of these drugs in each of the 7019 drug sets. To validate DrugPattern, we employed it for the prediction of the effects of oxidized low-density lipoprotein (oxLDL), a factor expected to be deleterious. We predicted that oxLDL has beneficial effects on some diseases, most of which were supported by evidence in the literature. Because DrugPattern predicted the potential beneficial effects of oxLDL in type 2 diabetes (T2D), animal experiments were then performed to further verify this prediction. As a result, the experimental evidences validated the DrugPattern prediction that oxLDL indeed has beneficial effects on T2D in the case of energy restriction. These data confirmed the prediction accuracy of our approach and revealed unexpected protective roles for oxLDL in various diseases. This study provides a tool to infer patterns and rules in biomedical datasets based on drug set enrichment analysis. DrugPattern is available at http://www.cuilab.cn/drugpattern.     

VISUAL CHARACTERIZATION OF THE ESTHETIC QUALITY OF THE ROSEBUSH

Since its introduction into the analysis of foodstuffs, sensory analysis has been applied in several contexts. This work seeks to widen the field of sensory analysis to include ornamental plants and to characterize their esthetic quality. Using the rosebush as a plant model, an attribute generation protocol is proposed in order to develop a conventional profile of such products. Further to statistical treatments aiming to verify the unambiguity, discrimination and independence of these attributes, a reduced list of 18 attributes has been set up. These attributes make up the very core of the conventional profiling studies currently undertaken .

PRACTICAL APPLICATIONS

The generation of a list of attributes that is not too long, in order to describe plants as exhaustively as possible, is one of the first steps of extending sensory analysis methods to ornamental horticulture. This list will be used to train a panel of assessors to characterize the rosebush.
Two applications are in progress. The first application consists of evaluating the impact of nitrogen nutrition on the visual quality of the rosebush. The second has the objective of determining which characteristics influence consumer preferences.     

Waiting list for kidney transplant. Some patients wait too long.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.     

The Default Value Approach to the Precautionary Principle

In science, when information is lacking, the reasonable response is to suspend judgement. When incomplete scientific information is to be used for decision-making purposes, such as regulation, the option of suspending judgement is not available. In such situations the precautionary principle may be used. One of several problems with the precautionary principle is that it is poorly defined and difficult to operationalize. We propose a way of operationalizing the precautionary principle through assigning cautious default values to variables that are needed in the risk analysis but are nevertheless unknown. A formalized model is introduced, in which the precautionary principle is interpreted in terms of default values of chemicals regulation. Four different methods for choosing default values (positive list, negative list, statistical expectation, and precaution) are discussed.     

A new paradigm for graduate research and training in the biomedical sciences and engineering

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.     

Pathway-based Analysis Tools for Complex Diseases:A Review

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehen- sive understanding of the molecular mechanisms underlying complex diseases. Extensive studies uti- lizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available path- way-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are dis- cussed. This review will provide a useful guide to dissect complex diseases.     

Whether or not to treat pneumonia curatively in (demented) psychogeriatric patients: evaluation of a guideline for nursing home physicians

A guideline was developed to support decision-making about whether or not to treat pneumonia curatively in psychogeriatric (demented) nursing home patients. This guideline was developed as a 'checklist of considerations', primarily of the ethical and legal aspects of decision-making. Nursing home physicians used and evaluated the list. The list's acceptance was assessed by measuring the frequency of the list's use, and judgements of the list's contents and 'usefulness'. The list was used in 50 out of 58 participating nursing homes, in 47% of the 489 psychogeriatric patients in whom pneumonia occurred. The list was found somewhat to very useful to support decision-making in 47% of 107 individual patients. For the targeted patient category as a whole, 85% of 48 physicians who were asked retrospectively (one physician per home) found the list somewhat to very useful. The content of the list was judged favourably. In conclusion, the nursing home physicians accepted the considerations of the checklist as a basis for decision-making on whether or not to treat pneumonia curatively in psychogeriatric patients. In the future, the format of the list can be adapted for use in diverse clinical situations. Suggestions are provided to increase user friendliness and usefulness.     

生物医学工程的研究范围

“生物医学工程”这个词汇蕴含了三个专业领域的相互影响：生物学（最广义的范围讲是基于物理学和化学的一门基础科学）、医学（治疗疾病的科学）和工程学（设计及建造对人类有用的物品的科学）。在20世纪50年代中期,我被任命组建一个实验室,这个实验室需要结合这三大学科,并致力于听觉研究。在过去的50年中,我们的实验室（由麻省理工大学、哈佛大学、麻省总医院及麻省眼耳医院共同管理）树立了一个优秀的范例,证明虽然有一些实际的困难,科学家、临床医师和工程师们仍然可以很好地合作。我们的经验之一是,往往一些最成功的发现是基于对基本科学知识的发展,而不是来源于对特定临床需要的靶向性研究。然而,“研究与发展”常常需要有技术创新教育背景,并能与数个领域的专家充分交流的特殊工作人员。因此,在目前这个环境与社会问题需要传统意义上非生物医学工程领域的技术专家的时代,生物医学工程师的培养问题及资源应如何在发达国家与发展中国家之间分配的问题的探讨,都具有十分重要的现实意义。     

Biological approaches for addressing the grand challenge of providing access to clean drinking water

The U.S. National Academy of Engineering (NAE) recently published a document presenting "Grand Challenges for Engineering". This list was proposed by leading engineers and scientists from around the world at the request of the U.S. National Science Foundation (NSF). Fourteen topics were selected for these grand challenges, and at least seven can be addressed using the tools and methods of biological engineering. Here we describe how biological engineers can address the challenge of providing access to clean drinking water. This issue must be addressed in part by removing or inactivating microbial and chemical contaminants in order to properly deliver water safe for human consumption. Despite many advances in technologies this challenge is expanding due to increased pressure on fresh water supplies and to new opportunities for growth of potentially pathogenic organisms.     

Protein production and purification

In selecting a method to produce a recombinant protein, a researcher is faced with a bewildering array of choices as to where to start. To facilitate decision-making, we describe a consensus 'what to try first' strategy based on our collective analysis of the expression and purification of over 10,000 different proteins. This review presents methods that could be applied at the outset of any project, a prioritized list of alternate strategies and a list of pitfalls that trip many new investigators.     

An Interdisciplinary Perspective on Carbon Capture and Storage Assessment Methods

Climate change is one of the most serious threats facing humankind. Mitigating climate change will require a suite of actions to reduce greenhouse gas emissions. Carbon capture and storage (CCS) is a new technology aimed at mitigating climate change by capturing and storing carbon dioxide, typically in deep geological reservoirs. CCS has risks characteristic of new technologies, as well as risks unique to this technology and its application. Large‐scale CCS decision making is complex, encompassing environmental, social, and economic considerations and requiring the risks to be taken into consideration. CCS projects have been cancelled as a result of inadequate assessments of risks. To date, studies assessing CCS have been limited mostly to environmental, social, and economic fields in isolation from each other, predominantly using life cycle assessments (LCAs), cost benefit analyses (CBAs), or surveys of public perception. LCAs, CBAs, and surveys of public perception all have limitations for assessing difficult multifaceted problems. Incompatibilities across CCS assessment methods have hindered the comparison of the results across these single‐discipline studies and limited the possibility of drawing broader conclusions about CCS development. More standardization across assessment methods, study assumptions, functional units, and assessment criteria for CCS could be beneficial to the integration of multiple study results. We propose a set of criteria, which decision analysts could use to develop CCS‐project–specific criteria lists in order to comprehensively assess a CCS project's viability. This list was created by determining the frequency of use of each criterion in recent studies, with a focus on their use across disciplines.     

Review: Diagnosis and treatment of dementia: 2. Diagnosis

Background

Dementia can now be accurately diagnosed through clinical evaluation, cognitive screening, basic laboratory evaluation and structural imaging. A large number of ancillary techniques are also available to aid in diagnosis, but their role in the armamentarium of family physicians remains controversial. In this article, we provide physicians with practical guidance on the diagnosis of dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006.

Methods

We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that pertained to key diagnostic issues in dementia. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.

Results

Of the 1591 articles we identified on all aspects of dementia diagnosis, 1095 met our inclusion criteria; 620 were deemed to be of good or fair quality. From a synthesis of the evidence in these studies, we made 32 recommendations related to the diagnosis of dementia. There are clinical criteria for diagnosing most forms of dementia. A standard diagnostic evaluation can be performd by family physicians over multiple visits. It involves a clinical history (from patient and caregiver), a physical examination and brief cognitive testing. A list of core laboratory tests is recommended. Structural imaging with computed tomography or magnetic resonance imaging is recommended in selected cases to rule out treatable causes of dementia or to rule in cerebrovascular disease. There is insufficient evidence to recommend routine functional imaging, measurement of biomarkers or neuropsychologic testing.

Interpretation

The diagnosis of dementia remains clinically integrative based on history, physical examination and brief cognitive testing. A number of core laboratory tests are also recommended. Structural neuroimaging is advised in selected cases. Other diagnostic approaches, including functional neuroimaging, neuropsychological testing and measurement of biomarkers, have shown promise but are not yet recommended for routine use by family physicians.     

Laboratory Design for Microbiological Safety

Of the large amount of funds spent each year in this country on construction and remodeling of biomedical research facilities, a significant portion is directed to laboratories handling infectious microorganisms. This paper is intended for the scientific administrators, architects, and engineers concerned with the design of new microbiological facilities. It develops and explains the concept of primary and secondary barriers for the containment of microorganisms. The basic objectives of a microbiological research laboratory, (i) protection of the experimenter and staff, (ii) protection of the surrounding community, and (iii) maintenance of experimental validity, are defined. In the design of a new infectious-disease research laboratory, early identification should be made of the five functional zones of the facility and their relation to each other. The following five zones and design criteria applicable to each are discussed: clean and transition, research area, animal holding and research area, laboratory support, engineering support. The magnitude of equipment and design criteria which are necessary to integrate these five zones into an efficient and safe facility are delineated.     

Combining Population Viability Analysis with Decision Analysis

Management of endangered species requires methods to assess the effects of strategies, providing a basis for deciding on a best course of action. An important component of assessment is population viability analysis (PVA). The latter may be formally implemented through decision analysis (DA). These methods are most useful for conservation when used in conjunction. In this paper we outline the objectives and the potential of both frameworks and their overlaps. Both are particularly helpful when dealing with uncertainty. A major problem for conservation decision-making is the interpretation of observations and scientific measurements. This paper considers probabilistic and non-probabilistic approaches to assessment and decision-making and recommends appropriate contexts for alternative approaches.     

Selecting biological indicators for monitoring soils: A framework for balancing scientific and technical opinion to assist policy development

Soils are one of the most important features of the natural capital of terrestrial ecosystems. There is a strong and increasing policy requirement for effective monitoring of soils at local, regional and national-scales. However, it remains unclear which properties of soils are most appropriately monitored. This is partly due to the wide range of goods and services that soils provide, but also their inherent chemical, physical and biological complexity. Given that the biota plays such fundamental roles in the majority of ecosystem services provided by soils, biological properties are logical candidates as effective indicators, to complement soil physico-chemical properties. A plethora of biological methods have been suggested as indicators for monitoring soils but few are used in national-scale monitoring or are published as international standards. A framework for selecting ecologically relevant biological indicators of soil quality, for national-scale soil monitoring, that cover the range of functions and services of soil was devised. The literature was surveyed to identify 183 candidate biological indicators which were then scored by experts and stakeholders against a wide range of scientific and technical criteria. The framework used the scores and weightings to then rank, prioritise and select the indicators. This semi-objective approach using a “logical sieve” allowed repeated iterations to take account of end-user requirements and expert opinion. A ranked list of 21 indicators was produced that covered a range of genotypic-, phenotypic- and functional-based indicators for different trophic groups. Four of these were not deemed sufficiently robust for ready deployment in a national-scale monitoring scheme without further methodological development. The suite of indicators identified offers the strongest potential candidates for deployment in national-scale soil monitoring schemes. However, standard operating procedures, their inherent sensitivity, ability to discriminate between soil:land use combinations, ecological interpretation all need to be confirmed. The power of the approach adopted here is that it provides a clear record and audit trail on the decision-making process, enables different priorities to be set contingent on the nature of the desired monitoring, and can direct and allow the inclusion of further methods or indicators into the framework.     

Aus der Frühgeschichte des Verbandes Deutscher Zoodirektoren (VDZ) e.V. – Aus den Archiven des Zoologischen Gartens Breslau/Wrocław

The early history of the VDZ is nearly unknown. Surprisingly many historical materials of great value were discovered while reorganizing the library and archives of Wroc?aw (Breslau) Zoo. One of these discoveries is the nearly full set of the minutes from the meetings of the directors of German zoos starting from the first meeting in 1887 up to the 41st meeting held in 1929. To fill in the gap of the knowlegde about the history of VDZ we give a list of the meetings with some citations of each minutes. The full and complete list of all the meetings from the years 1887 – 1929 is given, with the dates, place and list of the participants. All names, titles and numeration cited here are exactly as printed in the original minutes. Also the citations, randomly derived from the minutes are given here exactly as in the original minutes.     

Genetik des Prostatakarzinoms

Prostate cancer is the most frequent malignancy in males and its etiology is strongly influenced by genetic factors. Nevertheless, no mutated genes which could be used for diagnosis have been identified in a major proportion of familial cases. Three genes with germline mutations have been identified after linkage analysis (ELAC2, RNASEL, MSR1), but these mutations are very rare and their penetrance is not well defined. The association of most genes with genetic variants is weak, and only BRCA2/familial breast cancer is of clinical relevance. As a consequence of the extreme genetic heterogeneity, diagnostic tools are not available and genetic counseling has to rely on risk estimates from pedigree data in which a single affected first degree relative indicates a relevant risk.