Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically diagnosed as abnormally high urinary albumin excretion rate (AER). We hypothesize that subtle changes in the urine metabolome precede the clinically significant rise in AER. To test this, 52 type 1 diabetic patients were recruited by the FinnDiane study that had normal AER (normoalbuminuric). After an average of 5.5 years of follow-up half of the subjects (26) progressed from normal AER to microalbuminuria or DKD (macroalbuminuria), the other half remained normoalbuminuric. The objective of this study is to discover urinary biomarkers that differentiate the progressive form of albuminuria from non-progressive form of albuminuria in humans. Metabolite profiles of baseline 24 h urine samples were obtained by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) to detect potential early indicators of pathological changes. Multivariate logistic regression modeling of the metabolomics data resulted in a profile of metabolites that separated those patients that progressed from normoalbuminuric AER to microalbuminuric AER from those patients that maintained normoalbuminuric AER with an accuracy of 75% and a precision of 73%. As this data and samples are from an actual patient population and as such, gathered within a less controlled environment it is striking to see that within this profile a number of metabolites (identified as early indicators) have been associated with DKD already in literature, but also that new candidate biomarkers were found. The discriminating metabolites included acyl-carnitines, acyl-glycines and metabolites related to tryptophan metabolism. We found candidate biomarkers that were univariately significant different. This study demonstrates the potential of multivariate data analysis and metabolomics in the field of diabetic complications, and suggests several metabolic pathways relevant for further biological studies

Understanding political responsibility in corporate citizenship: towards a shared responsibility for the common good

In this article, we explore the debate on corporate citizenship and the role of business in global governance. In the debate on political corporate social responsibility it is assumed that under globalization business is taking up a greater political role. Apart from economic responsibilities firms assume political responsibilities taking up traditional governmental tasks such as regulation of business and provision of public goods. We contrast this with a subsidiarity-based approach to governance, in which firms are seen as intermediate actors who have political co-responsibilities in society endowed upon them by (inter)national governmental institutions. We argue that both approaches face conceptual and empirical problems, and do not make clear the content and scope of political corporate responsibility. Based on Iris Marion Young’s account of political responsibility we argue that corporate actors and governmental actors have a shared responsibility to tackle societal problems. Taking political corporate responsibility not only entails engaging in private action or engaging in public–private partnerships, but it also includes aiding governmental actors to remedy injustice or even create public institutions where they do not yet exist. By adding this perspective we contribute to the debate on responsibility in corporate citizenship and clarify the political role business can play in global governance.</p

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

Philosophical racism and ubuntu: In dialogue with Mogobe Ramose

This article discusses two complementary themes that play an important role in contemporary South African political philosophy: (1) the racist tradition in Western philosophy; and (2) the role of ubuntu in regaining an authentic African identity, which was systematically suppressed during the colonial past and apartheid. These are also leading themes in Mogobe Ramose’s African Philosophy Through Ubuntu. The first part concentrates on John Locke. It discusses the thesis that the reprehensible racism of many founders of liberal political philosophy has lethally infected liberal theory

Les tons du langage tambouriné et les tons du langage parlé. Texte inédit du Père Placide Tempels, ofm. Introduction et traduction par A.J. Smet cp

A.J. Smet présente, en traduction française, un texte inédit de Placide Tempels concernant la relation entre les tons du langage tambouriné et ceux du langage parlé. Ce texte est à l'origine de la correspondance entre Tempels et Hulstaert. Cette correspondance a eu une influence certaine sur la rédaction de la "Philosophie bantoue" de Tempels. Quant aux tons, Tempels pose qu'en tshiluba, les deux systèmes diffèrent notablement ; ce qui est combattu par Hulstaert pour les langues lomongo et apparentées. Il en déduit qu'il existe une distinction entre les Bantu du Sud d'une part et les Bantu du Nord et les Soudanais de l'autre. Dans un post-scriptum, A.J. Smet publie quelques extraits d'études linguistiques qui appuient la thèse de Tempels.A.J. Smet presents a French translation of an unpublished Dutch text by Placied Tempels concerning the relation between the tones of the drumbeat and the spoken language. This text inaugurated the correspondence between Tempels and Hulstaert. This correspondence had a certain influence on the writing of the "Bantu Philosophy" by Tempels. As for the tones, the position of Tempels who states that, in Tshiluba, the two systems differ considerably, is contested by Hulstaert for Lomongo and related languages. He deducts that a distinction exists between the Bantu of the South on the one hand and the Bantu of the North and the Sudanese on the other. In a postscriptum, Smet publishes some excerpts from linguistic studies which confirm Tempels's thesis. Keywords: Drum language, Hulstaert, lomongo, Possoz, Tempels, tonologie, tshiluba Annal Aequatoria Vol. 27 2006: pp. 467-47