Estimation of the frequency of isoform–genotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms

Estimates of the impact of apolipoprotein E (apo E) alleles coding for the three common isoforms on plasma lipid levels assume genetic homogeneity among the genotype classes. To test this assumption, we have determined the apo E genotype at the two common polymorphic sites (amino acids 112 and 158) by DNA amplification and hybridisation with allele‐specific oligoprobes, in 195 unrelated Caucasian participants of the Rochester Family Heart Study previously classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant samples were initially detected. Repeat typing of these samples by both methods resolved nine discrepancies and analysis of additional blood samples from the remaining five individuals eliminated a further four discrepancies. The only truly discordant allele was found in a female subject who had an E3 isoform with the common E2 (Cys 112 , Cys 158 ) genotype. Transmission of this allele from the mother was demonstrated. From these results, we estimate the frequency of discrepancies between isoforms and common genotypes to be 0.25% in this population. Allele misclassification was caused by poor amplification of the DNA in six samples and superimposition of glycosylated and nonglycosylated apo E isoforms on isoelectric focusing gels in five samples. We conclude that the assumption of genetic homogeneity among genotype classes is valid and that misclassification due to technical difficulties is more frequent than true discordancies. © 1992 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101763/1/1370090403_ftp.pd

Perturbation theory for anisotropic dielectric interfaces, and application to sub-pixel smoothing of discretized numerical methods

We derive a correct first-order perturbation theory in electromagnetism for cases where an interface between two anisotropic dielectric materials is slightly shifted. Most previous perturbative methods give incorrect results for this case, even to lowest order, because of the complicated discontinuous boundary conditions on the electric field at such an interface. Our final expression is simply a surface integral, over the material interface, of the continuous field components from the unperturbed structure. The derivation is based on a "localized" coordinate-transformation technique, which avoids both the problem of field discontinuities and the challenge of constructing an explicit coordinate transformation by taking a limit in which a coordinate perturbation is infinitesimally localized around the boundary. Not only is our result potentially useful in evaluating boundary perturbations, e.g. from fabrication imperfections, in highly anisotropic media such as many metamaterials, but it also has a direct application in numerical electromagnetism. In particular, we show how it leads to a sub-pixel smoothing scheme to ameliorate staircasing effects in discretized simulations of anisotropic media, in such a way as to greatly reduce the numerical errors compared to other proposed smoothing schemes.Comment: 10 page

Synthesis of accelerograms compatible with the Chinese GB 50011-2001 design spectrum via harmonic wavelets: artificial and historic records

A versatile approach is employed to generate artificial accelerograms which satisfy the compatibility criteria prescribed by the Chinese aseismic code provisions GB 50011-2001. In particular, a frequency dependent peak factor derived by means of appropriate Monte Carlo analyses is introduced to relate the GB 50011-2001 design spectrum to a parametrically defined evolutionary power spectrum (EPS). Special attention is given to the definition of the frequency content of the EPS in order to accommodate the mathematical form of the aforementioned design spectrum. Further, a one-to-one relationship is established between the parameter controlling the time-varying intensity of the EPS and the effective strong ground motion duration. Subsequently, an efficient auto-regressive moving-average (ARMA) filtering technique is utilized to generate ensembles of non-stationary artificial accelerograms whose average response spectrum is in a close agreement with the considered design spectrum. Furthermore, a harmonic wavelet based iterative scheme is adopted to modify these artificial signals so that a close matching of the signals’ response spectra with the GB 50011-2001 design spectrum is achieved on an individual basis. This is also done for field recorded accelerograms pertaining to the May, 2008 Wenchuan seismic event. In the process, zero-phase high-pass filtering is performed to accomplish proper baseline correction of the acquired spectrum compatible artificial and field accelerograms. Numerical results are given in a tabulated format to expedite their use in practice

Recruiting medical groups for research: relationships, reputation, requirements, rewards, reciprocity, resolution, and respect

BACKGROUND: In order to conduct good implementation science research, it will be necessary to recruit and obtain good cooperation and comprehensive information from complete medical practice organizations. The goal of this paper is to report an effective example of such a recruitment effort for a study of the organizational aspects of depression care quality. METHODS: There were 41 medical groups in the Minnesota region that were eligible for participation in the study because they had sufficient numbers of patients with depression. We documented the steps required to both recruit their participation in this study and obtain their completion of two questionnaire surveys and two telephone interviews. RESULTS: All 41 medical groups agreed to participate and consented to our use of confidential data about their care quality. In addition, all 82 medical directors and quality improvement coordinators completed the necessary questionnaires and interviews. The key factors explaining this success can be summarized as the seven R's: Relationships, Reputation, Requirements, Rewards, Reciprocity, Resolution, and Respect. CONCLUSION: While all studies will not have all of these factors in such good alignment, attention to them may be important to other efforts to add to our knowledge of implementation science

Interactive Visual Labelling versus Active Learning: An Experimental Comparison

Methods from supervised machine learning allow the classification of new data automatically and are tremendously helpful for data analysis. The quality of supervised maching learning depends not only on the type of algorithm used, but also on the quality of the labelled dataset used to train the classifier. Labelling instances in a training dataset is often done manually relying on selections and annotations by expert analysts, and is often a tedious and time-consuming process. Active learning algorithms can automatically determine a subset of data instances for which labels would provide useful input to the learning process. Interactive visual labelling techniques are a promising alternative, providing effective visual overviews from which an analyst can simultaneously explore data records and select items to a label. By putting the analyst in the loop, higher accuracy can be achieved in the resulting classifier. While initial results of interactive visual labelling techniques are promising in the sense that user labelling can improve supervised learning, many aspects of these techniques are still largely unexplored. This paper presents a study conducted using the mVis tool to compare three interactive visualisations, similarity map, scatterplot matrix (SPLOM), and parallel coordinates, with each other and with active learning for the purpose of labelling a multivariate dataset. The results show that all three interactive visual labelling techniques surpass active learning algorithms in terms of classifier accuracy, and that users subjectively prefer the similarity map over SPLOM and parallel coordinates for labelling. Users also employ different labelling strategies depending on the visualisation used

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Modelling innovative interventions for optimising healthy lifestyle promotion in primary health care: "Prescribe Vida Saludable" phase I research protocol

<p>Abstract</p> <p>Background</p> <p>The adoption of a healthy lifestyle, including physical activity, a balanced diet, a moderate alcohol consumption and abstinence from smoking, are associated with large decreases in the incidence and mortality rates for the most common chronic diseases. That is why primary health care (PHC) services are trying, so far with less success than desirable, to promote healthy lifestyles among patients. The objective of this study is to design and model, under a participative collaboration framework between clinicians and researchers, interventions that are feasible and sustainable for the promotion of healthy lifestyles in PHC.</p> <p>Methods and design</p> <p>Phase I formative research and a quasi-experimental evaluation of the modelling and planning process will be undertaken in eight primary care centres (PCCs) of the Basque Health Service – OSAKIDETZA, of which four centres will be assigned for convenience to the Intervention Group (the others being Controls). Twelve structured study, discussion and consensus sessions supported by reviews of the literature and relevant documents, will be undertaken throughout 12 months. The first four sessions, including a descriptive strategic needs assessment, will lead to the prioritisation of a health promotion aim in each centre. In the remaining eight sessions, collaborative design of intervention strategies, on the basis of a planning process and pilot trials, will be carried out. The impact of the formative process on the practice of healthy lifestyle promotion, attitude towards health promotion and other factors associated with the optimisation of preventive clinical practice will be assessed, through pre- and post-programme evaluations and comparisons of the indicators measured in professionals from the centres assigned to the Intervention or Control Groups.</p> <p>Discussion</p> <p>There are four necessary factors for the outcome to be successful and result in important changes: (1) the commitment of professional and community partners who are involved; (2) their competence for change; (3) the active cooperation and participation of the interdisciplinary partners involved throughout the process of change; and (4) the availability of resources necessary to facilitate the change.</p

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

<p>Abstract</p> <p>Background</p> <p>Alendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.</p> <p>Results</p> <p>Three simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.</p> <p>Conclusion</p> <p>The proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.</p> <p>Graphical abstract</p> <p><display-formula><graphic file="1752-153X-6-25-i3.gif"/></display-formula></p

Lanthanide compounds containing a benzo-15-crown-5 derivatised [60]fullerene and the related [Tb(H2O)(3)(NO3)(2)(acac)]. C14H20O5 supramolecular adduct

Novel lanthanum(III), europium(III) and terbium(III) compounds of a benzo-15-crown-5 [60]fulleropyrrolidine were isolated in the solid state and characterised using vibrational (infrared and Raman) spectroscopy and by 13C CP MAS NMR for the lanthanum(III) compound. The photoluminescence properties were investigated for the europium(III) and terbium(III) compounds. The related [Tb(H2O)3(NO3)2(acac)] C14H20O5 [where acac ¼ acetylacetonate and C14H20O5 ¼ benzo-15-crown-5] supramolecular adduct was isolated using similar synthetic conditions, in the absence of [60]fullerene, and its crystal structure used as a model for the coordination sphere of the lanthanide [60]fullerene derivatives, with further supporting evidence given by photoluminescence measurements

In vitro mycorrhization of micropropagated plants: studies on Castanea sativa Mill.

In vitro mycorrhization can be made by several axenic and nonaxenic techniques but criticism exists about their artificiality and inability to reproduce under natural conditions. However, artificial mycorrhization under controlled conditions can provide important information about the physiology of symbiosis. Micropropagated Castanea sativa plants were inoculated with the mycorrhizal fungus Pisolithus tinctorius after in vitro rooting. The mycorrhizal process was monitored at regular intervals in order to evaluate the mantle and hartig net formation, and the growth rates of mycorrhizal and nonmycorrhizal plants. Plant roots show fungal hyphae adhesion at the surface after 24 hours of mycorrhizal induction. After 20 days a mantle can be observed and a hartig net is forming although the morphology of the epidermal cells remains unaltered. At 30 days of root–fungus contact the hartig net is well developed and the epidermal cells are already enlarged. After 50 days of mycorrhizal induction, growth was higher for mycorrhizal plants than for nonmycorrhizal ones. The length of the major roots was lower in mycorrhizal plants after 40 days. Fresh and dry weights were higher in mycorrhizal plants after 30 days. The growth rates of chestnut mycorrhizal plants are in agreement with the morphological development of the mycorrhizal structures observed at each mycorrhizal time. The assessment of symbiotic establishment takes into account the formation of a mantle and a hartig net that were already developed at 30 days, when differences between fresh and dry weights of mycorrhizal and nonmycorrhizal plants can be quantified. In vitro conditions, mycorrhization influences plant physiology after 20 days of root–fungus contact, namely in terms of growth rates. Fresh and dry weights, heights, stem diameter and growth rates increased while major root growth rate decreased in mycorrhizal plants.Springe