A Novel Tandem Mass Spectrometry Method for Rapid Confirmation of Medium- and Very Long-Chain acyl-CoA Dehydrogenase Deficiency in Newborns

BACKGROUND:Newborn screening for medium- and very long-chain acyl-CoA dehydrogenase (MCAD and VLCAD, respectively) deficiency, using acylcarnitine profiling with tandem mass spectrometry, has increased the number of patients with fatty acid oxidation disorders due to the identification of additional milder, and so far silent, phenotypes. However, especially for VLCADD, the acylcarnitine profile can not constitute the sole parameter in order to reliably confirm disease. Therefore, we developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS) method to rapidly determine both MCAD- and/or VLCAD-activity in human lymphocytes in order to confirm diagnosis. METHODOLOGY:LC-MS/MS was used to measure MCAD- or VLCAD-catalyzed production of enoyl-CoA and hydroxyacyl-CoA, in human lymphocytes. PRINCIPAL FINDINGS:VLCAD activity in controls was 6.95+/-0.42 mU/mg (range 1.95 to 11.91 mU/mg). Residual VLCAD activity of 4 patients with confirmed VLCAD-deficiency was between 0.3 and 1.1%. Heterozygous ACADVL mutation carriers showed residual VLCAD activities of 23.7 to 54.2%. MCAD activity in controls was 2.38+/-0.18 mU/mg. In total, 28 patients with suspected MCAD-deficiency were assayed. Nearly all patients with residual MCAD activities below 2.5% were homozygous 985A>G carriers. MCAD-deficient patients with one other than the 985A>G mutation had higher MCAD residual activities, ranging from 5.7 to 13.9%. All patients with the 199T>C mutation had residual activities above 10%. CONCLUSIONS:Our newly developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes. Importantly, based on measured MCAD residual activities in correlation with genotype, new insights were obtained on the expected clinical phenotype

Search for dark matter candidates and large extra dimensions in events with a jet and missing transverse momentum with the ATLAS detector

Open Access, Copyright CERN, for the benefit of the ATLAS collaboration. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited

Parallel transmit pulse design for saturation homogeneity (PUSH) for magnetization transfer imaging at 7T.

PurposeThis work proposes a novel RF pulse design for parallel transmit (pTx) systems to obtain uniform saturation of semisolid magnetization for magnetization transfer (MT) contrast in the presence of transmit field B1+ inhomogeneities. The semisolid magnetization is usually modeled as being purely longitudinal, with the applied B1+ field saturating but not rotating its magnetization; thus, standard pTx pulse design methods do not apply.Theory and methodsPulse design for saturation homogeneity (PUSH) optimizes pTx RF pulses by considering uniformity of root-mean squared B1+ , B1rms , which relates to the rate of semisolid saturation. Here we considered designs consisting of a small number of spatially non-selective sub-pulses optimized over either a single 2D plane or 3D. Simulations and in vivo experiments on a 7T Terra system with an 8-TX Nova head coil in five subjects were carried out to study the homogenization of B1rms and of the MT contrast by acquiring MT ratio maps.ResultsSimulations and in vivo experiments showed up to six and two times more uniform B1rms compared to circular polarized (CP) mode for 2D and 3D optimizations, respectively. This translated into 4 and 1.25 times more uniform MT contrast, consistently for all subjects, where two sub-pulses were enough for the implementation and coil used.ConclusionThe proposed PUSH method obtains more uniform and higher MT contrast than CP mode within the same specific absorption rate (SAR) budget

Safety and efficacy of aneurysm treatment with WEB in the cumulative population of three prospective, multicenter series

Background Flow disruption with the WEB is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown a low complication rate with good efficacy. Purpose To report clinical and anatomical results of the WEB treatment in the cumulative population of three Good Clinical Practice (GCP) studies: WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm), French Observatory, and WEBCAST-2. Methods WEBCAST, French Observatory, and WEBCAST-2 are single-arm, prospective, multicenter, GCP studies dedicated to the evaluation of WEB treatment. Clinical data were independently evaluated. Postoperative and 1-year aneurysm occlusion was independently evaluated using the 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. Results The cumulative population comprised 168 patients with 169 aneurysms, including 112 female subjects (66.7%). The patients' ages ranged between 27 and 77 years (mean 55.5±10.2 years). Aneurysm locations were middle cerebral artery in 86/169 aneurysms (50.9%), anterior communicating artery in 36/169 (21.3%), basilar artery in 30/169 (17.8%), and internal carotid artery terminus in 17/169 (10.1%). The aneurysm was ruptured in 14/169 (8.3%). There was no mortality at 1 month and procedure/device-related morbidity was 1.2% (2/168). At 1 year, complete aneurysm occlusion was observed in 81/153 aneurysms (52.9%), neck remnant in 40/153 aneurysms (26.1%), and aneurysm remnant in 32/153 aneurysms (20.9%). Re-treatment was carried out in 6.9%. Conclusions This series is at the moment the largest prospective, multicenter, GCP series of patients with aneurysms treated with WEB. It shows the high safety and good mid-term efficacy of this treatment