An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids

Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described in a large family with a dominant inheritance pattern. The initial stage of the disease is dominated by frontal lobe symptoms that develop into a rapidly advancing encephalopathy with pyramidal, deep sensory, extrapyramidal and optic tract symptoms. Median survival is less than 10 years. Recently, pathogenic mutations in CSF1R were reported in a clinically and histologically similar leukoencephalopathy segregating in several families. Still, the cause of HDLS-S remained elusive since its initial description in 1984, with no CSF1R mutations identified in the family. Here we update the original findings associated with HDLS-S after a systematic and recent assessment of several family members. We also report the results from exome sequencing analyses indicating the p.Cys152Phe variant in the alanyl tRNA synthetase (AARS) gene as the probable cause of this disease. The variant affects an amino acid located in the aminoacylation domain of the protein and does not cause differences in splicing or expression in the brain. Brain pathology in one case after 10 years of disease duration showed the end stage of the disease to be characterized by widespread liquefaction of the white matter leaving only some macrophages and glial cells behind the centrifugally progressing front. These results point to AARS as a candidate gene for rapidly progressing adult-onset CSF1R-negative leukoencephalopathies

Ultrasound dating at 12-14 weeks of gestation. A prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies.

Objectives To determine the accuracy of established ultrasound dating formulae when used at 12-14 weeks of gestation. Methods One-hundred and sixty-seven singleton pregnancies conceived after in-vitro fertilization (IVF) underwent a dating scan at 12-14 weeks of gestation. Gestational age at the dating scan was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan. Gestational age according to oocyte retrieval was regarded as the true gestational age. True gestational age was compared to gestational age calculated on the basis of 21 dating formulae based on fetal crown-rump length (CRL) measurements and to three dating formulae based on fetal biparietal diameter (BPD) measurements. In a previous study the three BPD formulae tested here had been shown to be superior to four other BPD formulae when used at 12-14 weeks of gestation. The mean of the differences between estimated and true gestational age and their standard deviation (SD) were calculated for each formula. The SD of the differences was assumed to reflect random measurement error. Systematic measurement error was assumed to exist if zero lay outside the mean difference ± 2SE (SE: standard error of the mean). Results The three best CRL formulae were associated with mean (non-systematic) measurement errors of -0.0, -0.1 and -0.3 days, and the SD of the measurement errors of these formulae varied from 2.37 to 2.45. All but two of the remaining CRL formulae were associated with systematic over- or under-estimation of gestational age, and the SDs of their measurement error varied between 2.25 and 4.86 days. Dating formulae using BPD systematically underestimated gestational age by -0.4 to -0.7 days, and the SDs of their measurement errors varied from 1.86 to 2.09. Conclusions We have identified three BPD formulae that are suitable for dating at 12-14 weeks of gestation. They are superior to all 21 CRL formulae tested here, because their random measurement errors were much smaller than those of the three best CRL formulae. The small systematic negative measurement errors associated with the BPD formulae are likely to be clinically unimportant

Realising a single labour market for researchers: Report of the ERA Expert Group

It has become increasingly evident that a more concerted strategy is necessary to address the human resources needs of the European Research Area (ERA). Such a strategy should establish realistic goals and develop clear methods for their implementation. The present Report addresses the Policy Options that the Expert Group 'Realising a single labour market for researchers' (EG Researchers) has identified in order to ensure more attractive careers for researchers and to progressively eliminate the obstacles hampering their mobility. We have chosen an architectural image in order to highlight the complementary nature of the components of the tetrahedral structure that we have conceived. For each of the proposed four cornerstones we identify the obstacles and hindrances that, in our view, continue to hamper the development of ERA, and provide some 'case studies' in order to illustrate our concerns. We then provide Policy Options, some of which have already been successfully tested and could therefore be generalised almost immediately, others could be implemented progressively. The recommendations in this report are addressed to all bodies in receipt of public funds for research. This is meant to include the funding agencies who disburse funds and those who receive them, in the public and private sector (universities, research centres and companies). All must take individual and collective responsibility for the implementation of the recommendations; in our opinion they will determine whether Europe does indeed become a single labour market for researchers. We believe that the European Commission can take the lead by implementing the recommendations in the Seventh Framework Programme

Modeling Results of the Quench Behavior of a Nb-Ti Canted-Cosine-Theta Corrector Magnet for LHC

A newly designed superconducting magnet of the Canted-Cosine-Theta (CCT) type was developed as a result of a collaboration between Swedish universities (Uppsala and Linneaus) and Swedish industries. This magnet was designed to function as a replacement of the present LHC orbit corrector magnets, which are approaching their end of life due to the radiation load. As a result, the new CCT magnet was developed to be more radiation tolerant and to constitute a one-to-one replacement to the currently installed version, which is a 1 m long 70 mm double aperture dipole magnet. The final magnet, which is currently under construction, will be tested at FREIA laboratory at Uppsala University and generate a magnetic field of 3.3 T and an integrated field of 2.8 Tm at about 85 A. To examine the magnet quench behavior and to identify a suitable quench protection system, the 3D electro-magnetic and thermal behavior of the coil was modeled using the RAT-Raccoon software. Based on the simulation results, a Metrosil varistor was selected to protect the magnet during the test. In this article, we report the results of the numerical analysis. The magnet model is equipped with a spot heater to initialize the quench and the temperature and voltages are monitored during the avalanche effect. The simulated current decay and the hot-spot temperature are analyzed with a focus on the impact of quench-back on the magnet protection