6 research outputs found
“Letter to the King” By Jules Destry: from Separatism to Unitarism in Belgium
No full textContradictions between the regions of Belgium - Wallonia and Flanders - have a long history associated with uneven political, economic and cultural development of the territories, which in 1830 became parts of an independent state, the Kingdom of Belgium. The "Letter to the King", written by eminent Belgian politician and writer, socialist Jules Destree (1863 - 1936 gg.), is one of the most interesting sources on the history of Belgium of this period, It became a kind of manifesto of balance between the ideas of separatism and unitarianism. This article includes excerpts from the "Letter to the King", which were given for the first time in the author's Russian translation and conducted historical criticism of the source. The study is based on a set of scientific methods and approaches, including the principle of scientific objectivity and systematic approach, used in historical research. The main methods are problematic and historical-comparative analysis, classification and comparison of political and historical concepts. An external source of criticism included information about the place and the time of the creation of document, the biography of the author studies; internal critic source recreates the idea of the letter and the background of historical events. Prominent Belgian politician and writer, socialist Jules Destree (1863 - 1936), highly appreciated the personal qualities of King Albert I, appealed to his experience and political vision, describing all the problems Walloons faced in their opposition to the Flemish. Destree in his letter opposed the unequal development of the regions of Belgium and the protectionist policies of the central government in respect to the detriment of Flanders Wallonia. He summarized and formulated the factors that, in his opinion, interfere with the full development of his country. Destree pays great attention to linguistic differences, which were at the heart of conflicts between Walloons and Flemings, and are still shaken by Belgium. He reflects on the fact that the central government should be doing to reduce the national tensions that unites two people, and that the shares, which should be a system of education that future generations were able to overcome the historical alienation of such geographically close and ideologically distant peoples. Although Jules Destree firmly defends separatism idea for Wallonia as the only solution to the problem, however, by the end of his letter, reasoning it takes a more balanced position. The idea of a unitary state was not denied completely, but Destree emphasizes the importance of a balanced central government policy in relation to the regions in order to reduce internal tensions between the two nations. The ideas embodied in his "Letter to the King", formed the basis of the principles of peaceful co-existence of further autonomous regions as part of the union, which was manifested in the future during the First World War, when the Walloons and Flemings alongside confronted a common enemy
Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome (Genetics in Medicine, (2018), 10.1038/s41436-018-0330-z)
No full textThe original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article
The Transcriptomic and Genomic Analysis of Lamin A/C Expression in the Colon and in Colorectal Cancer
No full textLamins A and C, also known as A-type lamins, are type V nuclear intermediate filament proteins which form an interlacing meshwork of filaments subjacent to the inner nuclear membrane termed the nuclear lamina. A-type lamins have been implicated in DNA replication, gene transcription regulation, apoptosis, regulation of growth promoters and nuclear migration. Traditionally, expression of A-type lamins has been associated with differentiated cells. As such, mutations in A-type lamins have been associated with a diverse range of genetic diseases, including premature ageing syndromes and with increased proliferation, especially in tumours.
In colorectal cancer, expression of A-type lamins, have been shown to impart an adverse prognosis. In order to understand the underlying biological processes responsible for this adverse outcome in patients with colorectal cancer, I sought to clarify the expression profile of A-type lamins and their binding partners in normal colonic/rectal mucosa, prior to investigating the expression of A-type lamins in colorectal cancers. I used fresh tissue specimens obtained from patients with colorectal cancer for my experiments. A unique finding was the expression of lamin A in the putative stem cell niche of colonic / rectal mucosal crypts.
Further studies in the form of a microarray analysis, revealed a very complex picture of up regulation involving various signalling cascades in the cancer samples expressing A-type lamins. There was no evidence to suggest a direct involvement of A-type lamins influencing the Wnt signalling cascade, however, direct involvement of other signalling cascades, such as the IGF signalling cascade, Shh signalling cascade and TGF-β signalling cascades were noted. These signalling cascades were known to influence the Wnt signalling cascades and hence could play a crucial role in the pathogenesis of colorectal cancers expressing A-type lamins.
In addition to these important signalling cascades, other key genes involved in apoptosis, growth promoters, cell adhesion, stem cell regulation, oncogenes and tumour suppression, were noted to have a unique expression profile in the cancer sample expressing A-type lamins, not observed in the cancer sample lacking A-type lamin expression. These observations were suggestive of A-type lamins having a diverse range of actions via, as yet, undefined pathways. It would appear that A-type lamins were imparting a more motile, less adherent phenotype with stem cell like features in colorectal cancers expressing A-type lamins. This could explain the observed poor prognosis of patients with colorectal cancers expressing A-type lamins.
Creatine kinase brain (CKB), was also identified as an additional, potential, prognostic indicator in the Duke’s B group of patients with colorectal cancer expressing A-type lamins. This potential marker, in conjunction with A-type lamin expression could be used to identify a sub group of Duke’s B patients at high risk. Whether adjuvant therapy in this group would help improve their long term survival is unknown since no study has been done to assess this
Companies of clouds : the development of multilateral cultural cooperation in western European international organisations
No full textThis thesis traces the development of styles and theories of cultural cooperation from
the pre-World War II models developed by France and Britain in particular, through
the post-WWII international cooperation structures which included cultural
cooperation as part of their structures. Organisations considered include the
International Committee for Intellectual Cooperation, the Brussels Treaty
Organisation, the Council of Europe and the European Union, focusing primarily on
the non-educational or scientific aspects of cultural cooperation. Sources used include
documentation of the two latter bodies and the public records of the UK Foreign
Office and Ministry of Education.
Intellectual cooperation was launched under the auspices of the League of Nations as
a separate entity from the bilateral cultural relations of governments. Its tradition
continues to be powerfully felt in the activity of the Council of Europe, after WWII
the fulcrum of multilateral cultural cooperation. The thesis shows how it moved away
from acting as a counterpoint to political developments towards the creation of a
programme based on sociological study, which contained a strong element of
federalist ideology, developing its own orthodoxy of "cultural policy", until partly
"repossessed" in the 1990s by political imperatives.
The contrast with the tightly regulated European Union is marked, and shows in
certain respects a return to earlier experiments in cultural cooperation, which
developed most of its theory and practice in the pre-1992 era when the Community
Treaty did not provide for action in the field of culture. The thesis argues that the EU's
cultural programme is not a manifestation of a "Europeanisation" of cultural policy,
although policies elsewhere in the organisation may well have that effect, but of
multilateral cultural cooperation
Further delineation of the KAT6B molecular and phenotypic spectrum
No full textKAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
No full textBACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
