Cognitive and neurological outcome of patients in the Dutch pyridoxine-dependent epilepsy (PDE-ALDH7A1) cohort, a cross- sectional study

Item does not contain fulltextBACKGROUND: Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort. METHODS: Neurological outcome was assessed in 24 patients (age 1-26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed. RESULTS: Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ > 85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients. DISCUSSION: Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

&lt;p&gt;&lt;b&gt;Objectives&lt;/b&gt; The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt; The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.&lt;/p&gt

Scientists as Midwives to Cluster Emergence: An Institutional Work Framework

The question of how embedded actors can create institutions that support cluster emergence remains unsolved in the cluster and national innovation systems literature. The present paper extends the recent literature on institutional entrepreneurship and institutional work to solve this paradox of embedded agency in the context of science-based clusters. Building on a longitudinal single case study of a functional foods cluster in Finland, we present an institutional work framework for cluster formation. We argue that, in addition to ideational, material and bridging work, authentic leadership work is critical for cluster emergence. The results of the study highlight the opportunities that scientists have to act as midwives to cluster formation, but they also show that well-functioning clusters need a broader support base.Peer reviewe

Search for the Rare Decay B0_s -> phi mu^+ mu- with the D0 Detector

We present a search for the flavor-changing neutral current decay B0_s -> phi mu+ mu- using about 0.45 fb^-1 of data collected in p \bar p collisions at sqrt{s} =1.96 TeV with the D{\O}detector at the Fermilab Tevatron Collider. We find an upper limit on the branching ratio of this decay normalized to B0_s -> J/psi phi of B(B0_s -> phi mu+ mu-)/B(B0_s -> J/psi phi) < 4.4\times 10^{-3} at the 95% C.L. Using the central value of the world average branching fraction of B0_s -> J/psi phi, the limit corresponds to B(B0_s -> phi mu+ mu-) < 4.1 \times 10^{-6} at the 95% C.L., the most stringent upper bound to date.Comment: 7 pages, 2 figures, LaTeX, to be submitted to Physical Review Letter

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Plasma–wall interaction studies within the EUROfusion consortium : progress on plasma-facing components development and qualification

The provision of a particle and power exhaust solution which is compatible with first-wall components and edge-plasma conditions is a key area of present-day fusion research and mandatory for a successful o peration of ITER and DEMO. The work package plasma-facing components (WP PFC) within the European fusion programme complements with laboratory experiments, i.e. in linear plasma devices, electron and ion beam loading f acilities, the studies performed in toroidally confined magnetic devices, such as JET, ASDEX Upgrade, WEST etc. The connection of both groups is done via common physics and engineering studies, including the qualificat ion and specification of plasma-facing components, and by modelling codes that simulate edge-plasma conditions and the plasma–material interaction as well as the study of fundamental processes. WP PFC addresses these c ritical points in order to ensure reliable and efficient use of conventional, solid PFCs in ITER (Be and W) and DEMO (W and steel) with respect to heat-load capabilities (transient and steady-state heat and particle lo ads), lifetime estimates (erosion, material mixing and surface morphology), and safety aspects (fuel retention, fuel removal, material migration and dust formation) particularly for quasi-steady-state conditions. Alter native scenarios and concepts (liquid Sn or Li as PFCs) for DEMO are developed and tested in the event that the conventional solution turns out to not be functional. Here, we present an overview of the activities with an emphasis on a few key results: (i) the observed synergistic effects in particle and heat loading of ITER-grade W with the available set of exposition devices on material properties such as roughness, ductility and m icrostructure; (ii) the progress in understanding of fuel retention, diffusion and outgassing in different W-based materials, including the impact of damage and impurities like N; and (iii), the preferential sputtering of Fe in EUROFER steel providing an in situ W surface and a potential first-wall solution for DEMO.Peer reviewe