De novo mutation in SLC25A22 gene: expansion of the clinical and electroencephalographic phenotype

The SLC25A22 (Solute Carrier Family 25, Member 22) gene encodes for a mitochondrial glutamate/H+ symporter and is involved in the mitochondrial transport of metabolites across the mitochondrial membrane. We hereby report a 12-year-old girl presenting with early-onset epileptic encephalopathy, hypotonia, and global developmental delay. Whole exome sequencing identified a novel homozygous missense mutation in SLC25A22 gene (c.97A>G; p.Lys33Glu), as the likely cause of the disease. The phenotype of our patient and EEG recordings do not completely overlap with the phenotypes previously described, leading to a new and more complex form of disease associated with SLC25A22 variants, characterized by dyskinetic movements and oculogyric crisis

Computer model validation with functional output

A key question in evaluation of computer models is Does the computer model adequately represent reality? A six-step process for computer model validation is set out in Bayarri et al. [Technometrics 49 (2007) 138--154] (and briefly summarized below), based on comparison of computer model runs with field data of the process being modeled. The methodology is particularly suited to treating the major issues associated with the validation process: quantifying multiple sources of error and uncertainty in computer models; combining multiple sources of information; and being able to adapt to different, but related scenarios. Two complications that frequently arise in practice are the need to deal with highly irregular functional data and the need to acknowledge and incorporate uncertainty in the inputs. We develop methodology to deal with both complications. A key part of the approach utilizes a wavelet representation of the functional data, applies a hierarchical version of the scalar validation methodology to the wavelet coefficients, and transforms back, to ultimately compare computer model output with field output. The generality of the methodology is only limited by the capability of a combination of computational tools and the appropriateness of decompositions of the sort (wavelets) employed here. The methods and analyses we present are illustrated with a test bed dynamic stress analysis for a particular engineering system.Comment: Published in at http://dx.doi.org/10.1214/009053607000000163 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Bayesian Framework for Predicting Customer Need Distributions

Predicting future customer needs is critical when selecting a concept for a new product. Customer need prediction is challenging because customer needs may change as external factors that influence needs change over time. This paper proposes a Bayesian framework to predict future distribution of customer needs by incorporating forecasts of external factors and their corresponding accuracies. The framework is demonstrated by an illustrative example in which designers predict future distribution of a customer need ( Fuel Efficient ) based on forecast of an external factor (gasoline price index) and the accuracy of the forecast. The benefit of incorporating forecasts of the external factor on concept selection and a sensitivity analysis of concept selection on the accuracy of the forecast are demonstrated in the illustrative example. Copyright © 2010 by ASME

Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report

Summary: What is known and objective: Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. Case summary: A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. What is new and conclusion: Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spra

Calixpyrrole Derivatives: “Multi Hydrogen Bond” Catalysts for γ-Butenolide Synthesis

Calix[4]pyrrole (1), calix[2]m-benzo[4]pyrrole (2), 10α,20β- and 10α,20α- bis(4-nitrophenyl)-calix[4]pyrroles 3 and 4, respectively, were found to exhibit various organocatalytic activities in the diastereoselective vinylogous addition reaction of 2-trimethylsilyloxyfuran (TMSOF, 7) to aldehydes. The γ-hydroxybutenolide products are obtained in fairly good yields and with moderate diastereoselectivity. The structures of the catalysts, as well as the reaction conditions, strongly influence the efficiency of the reaction