Current evidence for treatment with nusinersen for spinal muscular atrophy : a systematic review

Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing

EWC confidential : confidentiality in European Works Councils and how representatives deal with it : case study and survey insights

The idea behind the establishment of European Works Councils (EWCs) is that these are bodies which should be informed and consulted on company decisions and actions. However, this flow of information is often disrupted by confidentiality constraints imposed by management. Three central research questions are: (1) what are the different practices of confidentiality and the withholding of information in EWCs; (2) what are the different handling strategies EWC representatives use in order to deal with confidential information; and (3) how do these handling strategies affect the functioning of the EWC and the employee representatives themselves? The survey findings generally confirm the observations based on the case studies: EWC members who think management withholds information are also more likely to feel limited in discussing information because of the 'confidential' labelling; at the same time, EWC members who think management shares all information also feel much more free to talk about that information

Drie jaar Centrale Archeologische Inventaris: een overzicht en stand van zaken

Inleidend artikel van het eerste CAI-rapport uit 2004. Een stand van zaken na drie jaar inventarisatie (2001-2004)

Analyse van de morfologie en bewaringstoestand van een deel van het Romeinse aquaduct van Tongeren (prov. Limburg) met gebruik van het DHMV en erosiemodellering

An analysis of the morphology and preservation of a part of the Roman Aqueduct of Tongeren (prov. of Limburg) using Lidar measurements and erosion modelling. Between 2000 and 2004 the Flemish government ordered the creation of the so-called DTM-Flanders, mainly to support Flanders flood prevention policy. The DTM, based on lidar data, is available for the whole of Flanders, with a resolution of one measure point per 20 m². This article discusses the use of this instrument and a number of derivative products (water-, tillageand combined erosion models, flow accumulation modelling), combined with other geodata (aerial photographs, soil map) and earlier archaeological observations, for the evaluation of the preservation of the Roman aqueduct of Tongeren

Neolithic pottery finds at the wetland site of Bazel-Kruibeke (Flanders, Belgium): evidence of long-distance forager-farmer contact during the late 6th and 5th millennium cal BC in the Rhine-Meuse-Scheldt area

The salvage excavation of the wetland site of Bazel-Kruibeke yielded the first firm evidence of forager-farmer contact in the Scheldt valley already from the late LBK onwards. From then on contact most likely gradually increased leading to a piecemeal introduction of Neolithic commodities and knowledge. Around the middle of the 5th millennium cal BC the technique of pottery production and very likely also stock-breeding were adopted from contemporaneous farmer communities in the loess belonging to the (Epi-)Rossen tradition. At the transition from the 5th to the 4th millennium cal BC exchange with the Michelsberg/Spiere group culture led to an almost complete acculturation of these local communities probably also involving the introduction of agriculture in the Lower Scheldt basin

Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation

Central hypoventilation in adult patients is a rare life-threatening condition characterised by the loss of automatic breathing, more pronounced during sleep. In most cases, it is secondary to a brainstem lesion or to a primary pulmonary, cardiac or neuromuscular disease. More rarely, it can be a manifestation of congenital central hypoventilation syndrome (CCHS). We here describe a 25-year-old woman with severe central hypoventilation triggered by analgesics. Genetic analysis confirmed the diagnosis of adult-onset CCHS caused by a heterozygous de novo poly-alanine repeat expansion of the PHOX2B gene. She was treated with nocturnal non-invasive ventilation. We reviewed the literature and found 21 genetically confirmed adult-onset CCHS cases. Because of the risk of deleterious respiratory complications, adult-onset CCHS is an important differential diagnosis in patients with central hypoventilation