Disclosing conflicts of interest in German publications concerning health services research

<p>Abstract</p> <p>Background</p> <p>The influence of the pharmaceutical industry and other stakeholders on medical science has been increasingly criticised. When dealing with conflicts of interest in scientific publications it is important to ensure the best possible transparency. The objective of this work is to examine the disclosure practice of financial and non-financial conflicts of interest in German language publications concerning health services research for the first time.</p> <p>Methods</p> <p>We performed a systematic literature search in the PubMed data base using the MeSH term "health services research". The review was conducted on July 10, 2006, setting the limits "dates: published in the last 2 years" and "languages: German" (only articles with abstracts). 124 articles in 31 magazines were found. In the magazines the instructions for authors were examined as to whether a statement on conflicts of interest is expected – and if, in which form. Regarding the articles in the journals which require a statement, we examined whether the statement is explicitly published. The results are descriptively represented.</p> <p>Results</p> <p>13 magazines (42%) do not require any statement on conflicts of interest, whereas 18 journals (58%) expect a statement. Two of these 18 magazines refer explicitly to the uniform requirements of the <it>International Committee of the Medical Journal Editors </it>(ICMJE); the remaining 16 magazines give differently accentuated instructions on how to disclose conflicts of interest, whereby the focus is primarily on financial issues. A statement on conflicts of interest is explicitly published in 11 of the 71 articles (15%) which are found in the magazines that require a statement with the submission of a manuscript. Related to the total number of included articles, this means that the reader explicitly receives information on potential conflicts of interest in 9% of the cases (11 of 124 articles). Statements of others that are involved in the publication process (reviewers, editors) are not available in any of the articles examined.</p> <p>Conclusion</p> <p>A better sensitization for possible conflicts of interest in German publications concerning health services research is necessary. We suggest tightening the criteria for disclosure in the instructions for authors in the scientific journals. Among other things the equivalent consideration of financial and non-financial conflicts of interest as well as the obligatory publication of the statements should be part of good practice.</p

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing

Education, knowledge, and symbolic form

This article aims to introduce Ernst Cassirer, and his philosophy of symbolic form, to education studies, and, in doing so, to challenge the widespread but deeply flawed views of knowledge and so-called knowledge-based education that have shaped recent education policy in England. After sketching the current educational landscape, and then some of the main lines of flight in Cassirer’s work, time is given to a comparison with Heidegger—a more familiar figure by far in Anglophone philosophy than Cassirer, and who contributed to the displacement of Cassirer—in order to illustrate more clearly Cassirer’s original contribution, in particular to the relationship between knowledge and time. Cassirer’s view of knowledge stands in marked and critical contrast to that which has shaped recent educational reform in England, as he sees knowledge as a productive and expressive matter, and repudiates what I call the ‘building-blocks’ picture of knowledge and the hierarchisation of subject areas

Beyond a Dichotomy of Perspectives: Understanding Religion on the Basis of Paul Natorp’s Logic of Boundary

Based on Paul Natorp’s (1854–1924) late post-Neo-Kantian “Logic of Boundary” (German: “Grenzlogik”) I will offer a methodically controlled, non-reductionist and equally anti-essentialist reconstruction of the notion of religion. The pre-eminent objective of this reconstructive work is to overcome the well-known epistemological as well as methodological problem of a dichotomy between inside and outside perspectives on the subject of religion. Differently put, the objective consists in an attempt to demonstrate that there actually is “reason in religion” that is intellectually accessible for academic knowledge production. Following Natorp’s splendid formulation I will argue that religion operates neither ‘within’ nor ‘beyond’ the ‘boundary of humanity’ but exactly on [or ‘in’] this boundary. More precisely, I will explicate that religious praxis (including its specific production of knowledge) from Natorp’s standpoint can be understood as the performative realization, and habitual embodiment of the (contextually concrete) boundary of humanity or human reason itself. Due to its principial self-referentiality this boundary carries the crucial sense of a first and last positive and, therefore, both in theoretical terms definitive and in practical terms eminently instructive notion of boundary with no outside. This paradoxically all-enclosing, positive boundary, while explicitly including life’s inevitable negativity but, nonetheless, able to ideally sublate it, is the reason why the practice of religion, as empirical evidence unmistakably documents, can provide an incommensurably fulfilling, significant and meaningful closure with regards to the innermost self-perception of its practitioners (concerning their self-determination or agency)

Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration

Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter

Potential Relevance of α1-Adrenergic Receptor Autoantibodies in Refractory Hypertension

-AAB might have a mechanistic role and could represent a therapeutic target. in cardiomyocytes and induce mesentery artery segment contraction.-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension