Evaluation of a commercially available rapid urinary porphobilinogen test

Background: Demonstration of substantially increased urinary excretion of porphobilinogen is the cornerstone of diagnosing acute porphyria crisis. Because porphobilinogen testing is not implemented on clinical chemistry analysers, respective analyses are available in rather few clinical laboratories. The aim of this study was to critically describe and to evaluate a semi-quantitative rapid test for urinary porphobilinogen determination which is commercially available and recommended by the American Porphyria Foundation. Methods: Urinary samples from patients with acute intermittent porphyria and control samples were analysed and the semi-quantitative results were compared with the results obtained by a manual quantitative spectrophotometric method. Results: In all 32 samples studied, acceptable agreement between the results of the rapid test and the quantitative test was observed. Handling of the test was found to be convenient. Conclusions: The assay was found to be reliable and has the potential to increase the availability of porphobilinogen testing in the field

Incremental Mutual Information: A New Method for Characterizing the Strength and Dynamics of Connections in Neuronal Circuits

Understanding the computations performed by neuronal circuits requires characterizing the strength and dynamics of the connections between individual neurons. This characterization is typically achieved by measuring the correlation in the activity of two neurons. We have developed a new measure for studying connectivity in neuronal circuits based on information theory, the incremental mutual information (IMI). By conditioning out the temporal dependencies in the responses of individual neurons before measuring the dependency between them, IMI improves on standard correlation-based measures in several important ways: 1) it has the potential to disambiguate statistical dependencies that reflect the connection between neurons from those caused by other sources (e. g. shared inputs or intrinsic cellular or network mechanisms) provided that the dependencies have appropriate timescales, 2) for the study of early sensory systems, it does not require responses to repeated trials of identical stimulation, and 3) it does not assume that the connection between neurons is linear. We describe the theory and implementation of IMI in detail and demonstrate its utility on experimental recordings from the primate visual system

The (A)gamma-195 (C -> G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Hereditary persistence, of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma -globin genes persists into adult life. Several point mutations have been associated with the increased gamma -globin gene promoter activity. We evaluated the -195 (C-->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro, under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma -globin gene containing the -195 (C-->G) mutation. Furthermore: this is the first time that the -195 (C-->G) mutation of the (A)gamma -globin gene has been evaluated by in vitro gene expression.34448949

Harmonic Allocation of Authorship Credit: Source-Level Correction of Bibliometric Bias Assures Accurate Publication and Citation Analysis

Authorship credit for multi-authored scientific publications is routinely allocated either by issuing full publication credit repeatedly to all coauthors, or by dividing one credit equally among all coauthors. The ensuing inflationary and equalizing biases distort derived bibliometric measures of merit by systematically benefiting secondary authors at the expense of primary authors. Here I show how harmonic counting, which allocates credit according to authorship rank and the number of coauthors, provides simultaneous source-level correction for both biases as well as accommodating further decoding of byline information. I also demonstrate large and erratic effects of counting bias on the original h-index, and show how the harmonic version of the h-index provides unbiased bibliometric ranking of scientific merit while retaining the original's essential simplicity, transparency and intended fairness. Harmonic decoding of byline information resolves the conundrum of authorship credit allocation by providing a simple recipe for source-level correction of inflationary and equalizing bias. Harmonic counting could also offer unrivalled accuracy in automated assessments of scientific productivity, impact and achievement

The Importance of PRI Therapy for the Pastoral Counsellor

It is not always easy for pastoral counsellors to help people change. Often people have become stuck in their ways. Recent developments in the field of brain research help explain why change is difficult. This article discusses Past Reality Integration Therapy (PRI), a psychotherapeutic method that integrates recent findings of brain research and offers an important addition to the work of (pastoral) counsellors and psychotherapists. The use of this approach with Dutch students in their pastoral training is presented. Furthermore the importance of this new method for counsellors themselves, their clients and their work is discussed and some overall conclusions about the method and its practical application are presented

Metrics to evaluate research performance in academic institutions: A critique of ERA 2010 as applied in forestry and the indirect H2 index as a possible alternative

Excellence for Research in Australia (ERA) is an attempt by the Australian Research Council to rate Australian universities on a 5-point scale within 180 Fields of Research using metrics and peer evaluation by an evaluation committee. Some of the bibliometric data contributing to this ranking suffer statistical issues associated with skewed distributions. Other data are standardised year-by-year, placing undue emphasis on the most recent publications which may not yet have reliable citation patterns. The bibliometric data offered to the evaluation committees is extensive, but lacks effective syntheses such as the h-index and its variants. The indirect H2 index is objective, can be computed automatically and efficiently, is resistant to manipulation, and a good indicator of impact to assist the ERA evaluation committees and to similar evaluations internationally.Comment: 19 pages, 6 figures, 7 tables, appendice

Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.

A Novel Estimator for the Rate of Information Transfer by Continuous Signals

The information transfer rate provides an objective and rigorous way to quantify how much information is being transmitted through a communications channel whose input and output consist of time-varying signals. However, current estimators of information content in continuous signals are typically based on assumptions about the system's linearity and signal statistics, or they require prohibitive amounts of data. Here we present a novel information rate estimator without these limitations that is also optimized for computational efficiency. We validate the method with a simulated Gaussian information channel and demonstrate its performance with two example applications. Information transfer between the input and output signals of a nonlinear system is analyzed using a sensory receptor neuron as the model system. Then, a climate data set is analyzed to demonstrate that the method can be applied to a system based on two outputs generated by interrelated random processes. These analyses also demonstrate that the new method offers consistent performance in situations where classical methods fail. In addition to these examples, the method is applicable to a wide range of continuous time series commonly observed in the natural sciences, economics and engineering

Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>STEVOR proteins, encoded by the multicopy <it>stevor </it>gene family have no known biological functions. Their expression and unique locations in different parasite life cycle stages evoke multiple functionalities. Their abundance and hypervariability support a role in antigenic variation.</p> <p>Methods</p> <p>Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant antigens of this gene family and to follow changes in STEVOR expression in parasite populations panned on CSA or CD36 receptors. Immunofluorescence assays and immunoelectron microscopy were performed to study the subcellular localization of STEVOR proteins in different parasite stages. The capacity of the antibody to inhibit merozoite invasion of erythrocytes was assessed to determine whether STEVOR variants were involved in the invasion process.</p> <p>Results</p> <p>Antigenic variation of STEVORs at the protein level was observed in blood stage parasites. STEVOR variants were found to be present on the merozoite surface and in rhoptries. An insight into a participation in erythrocyte invasion was gained through an immunofluorescence analysis of a sequence of thin slides representing progressive steps in erythrocyte invasion. An interesting feature of the staining pattern was what appeared to be the release of STEVORs around the invading merozoites. Because the anti-STEVOR antibody did not inhibit invasion, the role of STEVORs in this process remains unknown.</p> <p>Conclusion</p> <p>The localization of STEVOR proteins to the merozoite surface and the rhoptries together with its prevalence as a released component in the invading merozoite suggest a role of these antigens in adhesion and/or immune evasion in the erythrocyte invasion process. These observations would also justify STEVORs for undergoing antigenic variation. Even though a role in erythrocyte invasion remains speculative, an association of members of the STEVOR protein family with invasion-related events has been shown.</p

Self-citations at the meso and individual levels: effects of different calculation methods

This paper focuses on the study of self-citations at the meso and micro (individual) levels, on the basis of an analysis of the production (1994–2004) of individual researchers working at the Spanish CSIC in the areas of Biology and Biomedicine and Material Sciences. Two different types of self-citations are described: author self-citations (citations received from the author him/herself) and co-author self-citations (citations received from the researchers’ co-authors but without his/her participation). Self-citations do not play a decisive role in the high citation scores of documents either at the individual or at the meso level, which are mainly due to external citations. At micro-level, the percentage of self-citations does not change by professional rank or age, but differences in the relative weight of author and co-author self-citations have been found. The percentage of co-author self-citations tends to decrease with age and professional rank while the percentage of author self-citations shows the opposite trend. Suppressing author self-citations from citation counts to prevent overblown self-citation practices may result in a higher reduction of citation numbers of old scientists and, particularly, of those in the highest categories. Author and co-author self-citations provide valuable information on the scientific communication process, but external citations are the most relevant for evaluative purposes. As a final recommendation, studies considering self-citations at the individual level should make clear whether author or total self-citations are used as these can affect researchers differently