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PubMed2002

[Statistics must be seen and scrutinized! Fundamental to the progress of medical science--yet neglected in medical journals].

Even the most respectable medical journals contain questionable conclusions, frequently based on erroneous statistical analyses. A common attitude among medical researchers seems to be that a deeper knowledge of statistical theory is not necessary--it might suffice to be acquainted with the statistical program packages. The most common statistical errors in medical manuscripts are related either to the structure of the data or to misunderstandings regarding the logic in some basic statistical procedures, especially significance analysis. Editors should designate professional statisticians to sort out those manuscripts which require further scrutiny from a statistical point of view. This can be organized on a consultative basis outside the framework of the traditional, "blinded" peer-review system. The assessments made by the medical journals have come to play a very specific role in the Swedish academic system with respect to doctoral dissertations. Further discussion of present procedures in this area would be highly desirable.

Data Interpretation, Statistical↗

PubMed1996

Telephone T.A.L.K.: a teaching/assessment tool for medical training.

An instrument for teaching and assessing interpersonal communication skills of physicians on the telephone was developed. A conceptual framework based on the acronym T.A.L.K. [Trust, Assert, Listen and K.I.S.S. (Know, Inquire, Solve, and Stroke)] was used for organizing 22 specific behaviors. Faculty gave feedback to residents using T.A.L.K. guidelines while listening to taped telephone calls of the residents T.A.L.K.ing with patients. A five-point scale enables the instrument to be used for skill assessment and program evaluation.

Clinical Competence↗

PubMed2006

Use of models to assess the reduction in contamination of water bodies by agricultural pesticides through the implementation of policy instruments: A case study of the Voluntary Initiative in the UK.

Through normal agricultural use, pesticides may reach environmental water bodies via several routes of entry. Various policies and initiatives exist to reduce the effects of pesticides in the environment. One such initiative in place in the UK is the Voluntary Initiative (VI). The VI is a voluntary scheme put forward by the Crop Protection Association with other crop protection and farming organisations to reduce the environmental impacts of pesticides. Mathematical models of pesticide fate can usefully be applied to examine the impact of factors influencing the contamination of water bodies by pesticides. The work reported here used water quality models to examine how changes in farmer behaviour could potentially impact pesticide contamination of environmental water bodies. As far as possible, uncalibrated, standard regulatory models were used. Where suitable models were not available, simple models were defined for the purposes of the study and calibrated using literature data. Scenarios were developed to represent different standards of practice with respect to pesticide user behaviour. The development of these scenarios was guided by the Crop Protection Management Plan (CPMP) aspect of the VI. A framework for the use of modelling in the evaluation of the VI is proposed. The results of the modelling study suggest that, in several areas, widespread adoption of the measures proposed in the VI could lead to reductions in pesticide contamination of environmental water bodies. These areas include pesticide contamination from farmyards, spray drift and field runoff. In other areas (including pesticide leaching to groundwater and contamination of surface water from field drains) the benefits that may potentially be gained from the VI are less clear. A framework to evaluate the VI should take into consideration the following aspects: (1) groundwater is more at risk when there is a combination of leachable compounds, vulnerable soils, shallow groundwater and high product usage; (2) surface water contamination from drains is most likely when heavy rain falls soon after application, the soils are vulnerable and product usage is high; (3) surface water contamination from drift is most likely when the distance between the spray boom and water body is small and product usage is high; (4) surface water contamination from farmyards is dependent on the nature of the farmyard surface, the competence of the spray operator and the level of product usage. Any policy or initiative to reduce pesticide contamination should be measured against farmer behaviour in these areas.

Agriculture↗

PubMed1996

Searching for resilience among African-American youth exposed to community violence: theoretical issues.

PURPOSE: The exploration of resilience factors which may moderate the impact of violence exposure on African-American youth living in high-crime neighborhoods has received scant research attention. Yet, how these adolescents appraise and cope with exposures to violent events has implications for social adaptation and resilience. This article attempts to organize diverse literatures and cross-disciplinary perspectives into an integrative framework for the study of resilience among African-American youth exposed to violence. METHODS: The search for protective factors requires critical examination of both the ethnocentric bias in traditional developmental frameworks and the decontextualization of sociocultural and environmental influences on adaptation. A paradigmatic refocusing is necessary, one which highlights the capacities for coping and adaptation resulting from the engagement of personal resources, family strengths, and community support systems. RESULTS: To facilitate this research, an appraisal and coping model of violence is presented. This model emphasizes the need to identify and assess the appraisal processes and coping strategies initiated by African-American families as they attempt to thrive amidst community violence. CONCLUSIONS: Protective factors, operative at different junctures and within different ecologies, may reduce the likelihood of maladaptation or promote social competence in African-American youth exposed to violence. This search for resilience must address the meaning of competence and mechanisms of familial and external support that are salient within the African-American community.

Adaptation, Psychological↗

PubMed1996

Affinity maturation of recombinant antibodies using E. coli mutator cells.

BACKGROUND: Phage libraries can display repertoires of antibodies which are greater in number than the mammalian immune response. However, the selected antibodies often have low binding affinity to their target antigen or hapten (KD below 10(-6) M), which is characteristic of the primary immune repertoire. There is a need for procedures to mimic somatic hypermutation through antigen driven affinity maturation, thereby increasing the affinity of selected immunoglobulins. OBJECTIVE: To investigate the effectiveness of mutation and affinity selection of recombinant antibody genes with mutator E. coli cells, incorporating phage-display strategies. STUDY DESIGN: Unique human scFvs were selected from a naive Fd-phage library. These genes were mutated by propagation in mutD5 mutator E. coli cells (mutD5-FIT) which were competent for Fd (M13) based phagemid transfections and generated point mutations (transversions and transitions) in the scFv genes. Individual phage-displayed scFvs were affinity selected from the mutation library and were assayed as soluble scFvs by ELISA and BIAcore for binding to antigen. RESULTS: The in vivo mutation of phage-displayed scFvs in E. coli mutD5-FIT, combined with affinity selection against antigen, produced scFv molecules with improved binding activity. The point mutations which resulted in single amino acid substitutions frequently produced ten fold increases in apparent binding affinity. Structural comparisons revealed that these point mutations were in framework regions (adjacent to the CDRs) and within the CDRs. In one case the apparent affinity of an anti-glycophorin scFv after mutation in the VL framework region close to CDR3 increased by 10(3). However, this increase in apparent affinity was accompanied by an increased propensity to dimerise and form aggregates. CONCLUSIONS: A strategy for the rapid affinity maturation of scFv and Fab antibody fragments has been developed which utilises mutator strains of E. coli and incorporates phage display of antibody repertoires (libraries).

Antibody Affinity↗

PubMed1996

Communication, accrual to clinical trials, and the physician-patient relationship: implications for training programs.

BACKGROUND: Previous studies have demonstrated that less than 20% of fully eligible patients participate in cancer clinical trials. One of the major factors determining whether patients will be successfully accrued to trials is the quality of the communication occurring between the physician and patient (and family members if present). The accrual process is embedded within the longer-term relationship between the physician and the patient. It is argued that the interaction occurring during the consent process is part of an "alliance building" that the physician and patient use to confront the uncertainty inherent in both the disease itself and the outcome of therapy. METHODS AND RESULTS: The authors describe the framework of a study currently under way in which they are tracking the variation in ways that this interaction is managed by a sample of oncologists and their patients. Physicians and patients are simultaneously filmed and viewed in a split-screen format. A coding system is being developed to analyze the congruence between physicians and patients as they encode and decode sequences of verbal and nonverbal messages. The goal is to understand how physicians and patients manage uncertainty related to the disease and its outcomes. CONCLUSIONS: The authors suggest implications of these observed patterns for the broader range of communicative competencies that medical students must learn.

Classification↗

PubMed1997

Determinants of regular source of care among homeless adults in Los Angeles.

OBJECTIVES: The authors explore the determinants of having a regular source of care in a community-based probability sample of homeless adults in Los Angeles. Results from this study should be more representative than those from previous studies of the homeless that are clinic- or shelter-based. In addition to those factors found to be barriers to regular sources of care in the general population, we hypothesized that psychosocial characteristics of the homeless and the homeless lifestyle would negatively impact their likelihood of having a regular source of care. METHODS: The authors conducted a multiple logistic regression to predict regular source of care among the homeless, using an adaptation of the Behavioral Model of health services utilization as an analytic framework. RESULTS: Fifty-seven percent of the sample reported that they had a regular source of care. Of those with a source of care, 30% reported a hospital outpatient department; 25% reported a community or homeless clinic; 23% reported a hospital emergency room; 14% reported a government clinic; and 9% reported a private physician's office as their source of care. Some factors found to be barriers to having a regular source of care in the general population (male, Hispanic, young age) also were barriers among homeless adults. Additional barriers in this sample included homelessness-related characteristics such as competing needs, long-term homelessness, and social isolation. Chronic mental illness and chronic substance dependence were not related to having a source of care among the homeless. Characteristics that increased the likelihood of having a regular source of care in the general population (poor health status, Medicaid) were not related to having a regular source of care among the homeless. CONCLUSIONS: In a context of limited resources, the distribution of regular source of care among the homeless appears to be highly inequitable. Although some of the characteristics identifying those with a regular source of care suggest differential patterns of behavior across subgroups, others suggest differential advantage in access to care and a lack of fit between the needs of the homeless and the organization of health services.

Adolescent↗

PubMed2006

Endogenous timing in competitive interactions among relatives.

Most evolutionary game theory models solve for equilibrium levels of some behaviour on the restrictive assumptions that players choose their actions simultaneously, and that a player cannot change its action after observing that of its opponent. An alternative framework is provided by sequential or 'Stackelberg' games in which one player commits to a 'first move' and the other has an opportunity to observe this move before choosing its response. Recent interest in the economic literature has focused on Stackelberg games which exhibit 'endogenous timing', i.e. games in which a leader and a follower arise spontaneously as a consequence of each player attempting to maximize its reward. Here, we provide the first demonstration of endogenous timing in an evolutionary context using a simple model of resource competition (the 'tug-of-war' model). We show that whenever two related individuals compete for a share of communal resources, both do best to adopt distinct roles in a sequential game rather than engage in simultaneous competition. Somewhat counterintuitively, the stable solution is for the weaker individual to act as leader and commit to a first move, because this arrangement leads to a lower total effort invested in competition. Endogenous timing offers a new explanation for the spontaneous emergence of leaders and followers in social groups, and highlights the benefits of commitment in social interaction.

Biological Evolution↗

PubMed1998

Curriculum integration in nutrition and mathematics.

Today's school-aged children face a multitude of health issues that affect their well-being and academic performance. Partnerships have developed between health and education agencies to help American children succeed at math and science and to prepare them to make healthful, lifelong decisions. Curriculum integration provides a framework for children to apply knowledge from several disciplines and to use this knowledge to solve real-life problems at work and at play. Goals for instruction focus on the needs not only of the individual but also of society. Nutrition science and mathematics form a natural partnership. Nutrition science incorporates numerous mathematical concepts and procedures such as sorting, classifying, statistics, probability, estimation, and rates and proportion. In preparation for participation in a global and technological society that will require citizens to be quantitative thinkers, educators must endeavor to assist all children in becoming adults who are mathematically literate and competent.

Adolescent↗

PubMed2006

Mémoire: A framework for semantic interoperability of case-based reasoning systems in biology and medicine.

OBJECTIVE: Mémoire is a framework for sharing and distributing case bases and case-based reasoning (CBR) systems in biology and medicine. METHODS AND MATERIAL: This paper first introduces the semantic Web approach to build a better Web where search engines, knowledge sources and servers, applications and services can live, work, and learn in cooperation. This semantic approach is particularly well suited for biomedical domains because significant ontologies have been developed there and constitute a sound basis for the standardization effort required for the semantic Web. Case-based reasoning systems in biomedicine have also benefited from these biomedical ontologies and models. RESULTS: This article demonstrates for three such systems how a semantics infused approach in CBR gives better, more accurate results in CBR. From this previous work on a semantic approach in CBR in biomedicine, the Mémoire framework has evolved. CONCLUSION: Mémoire proposes a unified OWL-based representation language for cases and case-based ontologies in biomedicine, where a Web Ontology Language (OWL) is a language to represent ontologies on the Web. Mémoire provides a set of tools for building case-based reasoning systems compliant with its language. Mémoire is extensible and can be adapted to different types of biomedical application domains, tasks, and environments. Mémoire will permit bridging the gap within the multiple case-based reasoning systems dedicated to a single domain, and make available to agents and Web services the case-based competency of the CBR systems adopting its interchange language. The approach could be extended to other application domains of CBR.

Artificial Intelligence↗

PubMed1996

The practitioner-teacher: a study in the introduction of mentors in the preregistration nurse education programme in Wales: Part 1.

This study focused on the introduction of mentors in the Common Foundation Programme of Project 2000 schemes of preregistration nurse education. The research, which was commissioned by the Department of Health Research and Development Division on behalf of the Welsh Office Nursing Division, began in February 1992 and was undertaken on an all-Wales basis. The completed report aims to provide policy makers with information relating to important issues which are central to the teaching and learning of nursing in clinical locations. This first paper discusses some background issues and gives a brief conceptual framework for considering policy reform, summarizes the research questions which emerged and describes the methods used to address them. The second paper (to appear in the next issue of the journal) will describe the key findings from the study and discuss some ensuing potential implications and considerations for all those involved in the preparation of future practitioners of nursing.

Clinical Competence↗

PubMed2005

Evaluation of chondroitin sulfate bioactivity in hippocampal neurones and the astrocyte cell line U373: influence of position of sulfate groups and charge density.

Chondroitin sulfates are linear polysaccharides of alternating glucuronic acid and N-acetylgalactosamine, sulfated in varying positions. They form the extracellular framework providing the information for the structural establishment of tissues in multicellular organisms. Growth cones of neurones modulate their outgrowth according to signals received from proteoglycans. The exact molecular structures behind these functions are not fully understood, but structural details of the carbohydrate backbone are crucial. In this report we have employed quantitative cytometry on hippocampal neurite outgrowth in the presence of chondroitin sulfate added in solution to determine the influence of the position and density of the sulfate groups of the N-acetyl-D-galactosamine-residues of chondroitin sulfates. It is of profound interest whether externally added chondroitin sulfates can compete with core protein bound chondroitin sulfate to modulate the effects of tissue-synthesized matrix. In series of microscopic images 3 parameters of neuritic outgrowth activity, neurite length, number of neurites and fasciculation (thickness of neurites) are analyzed at concentrations occurring in intact tissues. Fasciculation increased and number of neurites decreased with high di-sulfation. No significant differences on process length reduction were found between the isotypes. Specificity of effects found is emphasized, as no influence on cell proliferation with U373 human astrocyte cell line is detectable, while neurones clearly are inhibited. The IC30 and IC50 values of chondroitin sulfates isoforms are presented for neurones. The data indicate that the soluble fragments from chondroitin sulfate are actively modulating cell development. Besides dosage, sulfation density and position are relevant for effects of chondroitin sulfate in neuronal regenerative activity.

Animals↗

PubMed1996

Requirements for kissing-loop-mediated dimerization of human immunodeficiency virus RNA.

Sequences from the 5' end of type 1 human immunodeficiency virus RNA dimerize spontaneously in vitro in a reaction thought to mimic the initial step of genomic dimerization in vivo. Dimer initiation has been proposed to occur through a "kissing-loop" interaction involving a specific RNA stem-loop element designated SL1: the RNA strands first interact by base pairing through a six-base GC-rich palindrome in the loop of SL1, whose stems then isomerize to form a longer interstrand duplex. We now report a mutational analysis aimed at defining the features of SL1 RNA sequence and secondary structure required for in vitro dimer formation. Our results confirm that mutations which destroy complementarity in the SL1 loop abolish homodimer formation, but that certain complementary loop mutants can heterodimerize. However, complementarity was not sufficient to ensure dimerization, even between GC-rich loops, implying that specific loop sequences may be needed to maintain a conformation that is competent for initial dimer contact; the central GC pair of the loop palindrome appeared critical in this regard, as did two or three A residues which normally flank the palindrome. Neither the four-base bulge normally found in the SL1 stem nor the specific sequence of the stem itself was essential for the interaction; however, the stem structure was required, because interstrand complementarity alone did not support dimer formation. Electron microscopic analysis indicated that the RNA dimers formed in vitro morphologically resembled those isolated previously from retroviral particles. These results fully support the kissing-loop model and may provide a framework for systematically manipulating genomic dimerization in type 1 human immunodeficiency virus virions.

Base Sequence↗

PubMed2005

Hearing the patient's voice? Factors affecting the use of patient survey data in quality improvement.

OBJECTIVE: To develop a framework for understanding factors affecting the use of patient survey data in quality improvement. DESIGN: Qualitative interviews with senior health professionals and managers and a review of the literature. SETTING: A quality improvement collaborative in Minnesota, USA involving teams from eight medical groups, focusing on how to use patient survey data to improve patient centred care. PARTICIPANTS: Eight team leaders (medical, clinical improvement or service quality directors) and six team members (clinical improvement coordinators and managers). RESULTS: Respondents reported three types of barriers before the collaborative: organisational, professional and data related. Organisational barriers included lack of supporting values for patient centred care, competing priorities, and lack of an effective quality improvement infrastructure. Professional barriers included clinicians and staff not being used to focusing on patient interaction as a quality issue, individuals not necessarily having been selected, trained or supported to provide patient centred care, and scepticism, defensiveness or resistance to change following feedback. Data related barriers included lack of expertise with survey data, lack of timely and specific results, uncertainty over the effective interventions or time frames for improvement, and consequent risk of perceived low cost effectiveness of data collection. Factors that appeared to have promoted data use included board led strategies to change culture and create quality improvement forums, leadership from senior physicians and managers, and the persistence of quality improvement staff over several years in demonstrating change in other areas. CONCLUSION: Using patient survey data may require a more concerted effort than for other clinical data. Organisations may need to develop cultures that support patient centred care, quality improvement capacity, and to align professional receptiveness and leadership with technical expertise with the data.

Data Collection↗

PubMed1998

[Children experiencing pain and coping with it in situations of invasive diagnostics, therapies and care].

The opening of pediatric units for co-admission of parents brought a clear change in the professional understanding of pediatric nursing. In all areas of work this creates new challenges for pediatric nurses. Besides professional competences of caring for ill children they now require competences in guiding and counselling parents, offering them effective strategies for coping with stressful experiences in connection with the illness of their child. Quite often painful diagnostic or therapeutic interventions accompanying illness are extremely stress-laden, especially for young children. The pediatric nurse must transform these situations in a way that facilitates prevention and coping mechanisms for parents as well as for the affected children to support them in their coping strategies. This article legitimises the task of the pediatric nurse to counsel and guide parents of children in invasive painful situations in the light of Orem's Self-Care-Framework and from the perspective of developmental psychology. Cognitive as well as emotional coping mechanisms of children are presented, from which ways to counsel parents and to care for children in painful situations may be deduced. In a care situation trusting relationships between nurse, child and parents are essential. How children build trust should be a topic of research and discussion as well as the specific characteristics of a professional relationship between nurse and patient.

Adaptation, Psychological↗

PubMed1989

Artificial feeding for severely disoriented, elderly patients.

The issue of artificial feeding for patients with dementia who refuse feeding by hand is a wrenching emotional problem that can cloud clinical judgement. It is helpful to apply an analytic approach to decision making. There are five steps: gathering a comprehensive clinical database; defining the goal of treatment; knowing the treatment options available, their burdens and potential benefits; understanding the law; and defining the moral framework in which care is being given. Such an approach can be used to formulate a plan of treatment in the best interests of incompetent elderly patients who cannot speak for themselves.

Advance Directives↗

PubMed1989

Sterically hindered analogues of diacylglycerols. Synthesis, binding to the phorbol ester receptor and metabolism in A549 human lung carcinoma cells.

The 5 following compounds were synthesized in order to investigate the relationship between structure and ability of glyceride-type molecules to bind to the phorbol ester receptor: one dioctanoyl cyclohexane-1,2,4-triol, 2 isomeric methyl analogues of 1,2-dioctanoyl-sn-glycerol (diC8), one dimethyl and one cyclohexyl analogue of diC8. Their ability to compete with 3H-labelled phorbol-12,13-dibutyrate [( 3H]PDBu) for specific binding sites in intact A549 human-derived lung carcinoma cells and in a cytosolic cell extract was compared with that of diC8 and 12-O-tetradecanoylphorbol-13-acetate (TPA). The affinity of diC8 for the phorbol ester receptor was much weaker than that of TPA. The analogues in turn were less able than diC8 to compete with [3H]PDBu for receptor sites. Like diC8 and unlike TPA, the synthesized compounds inhibited cell growth only at those concentrations at which cytotoxicity was also apparent. DiC8 and its methyl and dimethyl derivates, but not the cyclohexyl derivative or the cyclohexanetriol diester, were metabolically removed from cellular incubates as measured by gas liquid chromatography. The results suggest that the binding of glyceride-type molecules to the phorbol ester receptor exhibits stringent specificity and that the design of novel potent agonists of phorbol esters might require the placement of the molecular features of diacylglycerols important for biological activity into a molecular framework which is more complicated than glycerol.

Caenorhabditis elegans Proteins↗

PubMed2005

The use of yeast mitochondria to study the properties of wild-type and mutant human mitochondrial ornithine transporter.

Yeast deletion models have general utility for the study of a variety of inherited metabolic disorders. Mutations in the mitochondrial ornithine transporter result in hyperammonemia, hyperornithinemia, homocitrullinuria syndrome, a disorder of the urea cycle. To study the effects of mutations in a model system that more closely resembles the in vivo environment, we have developed an expression system based on a yeast strain lacking its endogenous ornithine transporter homologue. Wild-type human ornithine transporter and a recurrent mutation, DeltaF 188, were expressed and characterized with this system. The wild-type transporter appeared to insert into yeast mitochondria in the same orientation as in mammalian mitochondria. It showed stereospecificity, strong antiport activity and ornithine transport was competed by citrulline and arginine. The DeltaF 188 mutant was not incorporated into the membrane to the same extent as wild type, but retained significant residual activity and lost stereospecificity. In these isolated mitochondria, samarium chloride was found to be a potent blocker of transport compared to previously reported sulfhydryl-based inhibitors. A low-affinity background transport activity that promoted the exchange of ornithine for either acidic or basic amino acids was observed. This yeast model can readily be extended to the study of protein:protein interactions. In this manner, the use of yeast deletion strains can serve as a general framework to perform metabolic pathway analysis.

Amino Acid Transport Systems, Basic↗

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