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Hoischen A.,A-Life Medical | Krumm N.,University of Washington | Eichler E.E.,Howard Hughes Medical Institute
Nature Neuroscience | Year: 2014

Advances in genome sequencing technologies have begun to revolutionize neurogenetics, allowing the full spectrum of genetic variation to be better understood in relation to disease. Exome sequencing of hundreds to thousands of samples from patients with autism spectrum disorder, intellectual disability, epilepsy and schizophrenia provides strong evidence of the importance of de novo and gene-disruptive events. There are now several hundred new candidate genes and targeted resequencing technologies that allow screening of dozens of genes in tens of thousands of individuals with high specificity and sensitivity. The decision of which genes to pursue depends on many factors, including recurrence, previous evidence of overlap with pathogenic copy number variants, the position of the mutation in the protein, the mutational burden among healthy individuals and membership of the candidate gene in disease-implicated protein networks. We discuss these emerging criteria for gene prioritization and the potential impact on the field of neuroscience. © 2014 Nature America, Inc.

Helleday T.,A-Life Medical | Eshtad S.,A-Life Medical | Nik-Zainal S.,Wellcome Trust Sanger Institute | Nik-Zainal S.,University of Cambridge
Nature Reviews Genetics | Year: 2014

The collective somatic mutations observed in a cancer are the outcome of multiple mutagenic processes that have been operative over the lifetime of a patient. Each process leaves a characteristic imprint-a mutational signature-on the cancer genome, which is defined by the type of DNA damage and DNA repair processes that result in base substitutions, insertions and deletions or structural variations. With the advent of whole-genome sequencing, researchers are identifying an increasing array of these signatures. Mutational signatures can be used as a physiological readout of the biological history of a cancer and also have potential use for discerning ongoing mutational processes from historical ones, thus possibly revealing new targets for anticancer therapies. © 2014 Macmillan Publishers Limited. All rights reserved.

Crosetto N.,University Utrecht | Bienko M.,A-Life Medical | Van Oudenaarden A.,University Utrecht
Nature Reviews Genetics | Year: 2015

Considerable progress in sequencing technologies makes it now possible to study the genomic and transcriptomic landscape of single cells. However, to better understand the complexity of multicellular organisms, we must devise ways to perform high-throughput measurements while preserving spatial information about the tissue context or subcellular localization of analysed nucleic acids. In this Innovation article, we summarize pioneering technologies that enable spatially resolved transcriptomics and discuss how these methods have the potential to extend beyond transcriptomics to encompass spatially resolved genomics, proteomics and possibly other omic disciplines. © 2014 Macmillan Publishers Limited. All rights reserved.

Sandhoff K.,A-Life Medical
Biochemical Society Transactions | Year: 2013

Lysosomes are cellular stomachs. They degrade macromolecules and release their components as nutrients into the cytosol. Digestion of sphingolipids and other membrane lipids occurs at luminal intraendosomal vesicles and IMs (intraendosomal membranes). Sphingolipid and membrane digestion needs catabolic hydrolases with the help of lipid-binding proteins [SAPs (sphingolipid activator proteins)] and anionic lipids such as BMP [bis(monoacylglycero)phosphate]. Inherited defects of hydrolases or SAPs or uptake of cationic amphiphilic drugs cause lipid accumulation, eventually leading to death, especially in inherited sphingolipid storage diseases. IMs are formed during endocytosis and their lipid composition is adjusted for degradation. Their cholesterol content, which stabilizes membranes, decreases and the level of negatively charged BMP, which stimulates sphingolipid degradation, increases. At the level of late endosomes, cholesterol is transported out of the luminal vesicles preferentially by cholesterol-binding proteins, NPC (Niemann-Pick type C)-2 and NPC-1. Their defects lead to an endolysosomal accumulation of cholesterol and sphingolipids in Niemann-Pick type C disease. BMP and ceramide stimulate NPC-2-mediated cholesterol transfer, whereas sphingomyelin inhibits it. Anionic membrane lipids also activate sphingomyelin degradation by ASM (acid sphingomyelinase), facilitating cholesterol export by NPC-2. ASM is a non-specific phospholipase C and degrades more than 23 phospholipids. SAPs are membrane-perturbing proteins which solubilize lipids, facilitating glycolipid digestion by presenting them to soluble catabolic enzymes at acidic pH. High BMP and low cholesterol levels favour lipid extraction and membrane disintegration by saposin A and B. The simultaneous inherited defect of saposins A-D causes a severe membrane and sphingolipid storage disease, also disrupting the water permeability barrier of the skin. © 2013 Biochemical Society.

Computer-based, natural language processing systems and methods are provided for review of clinical documentation and other medical records, and for clinical documentation improvement. The systems and methods are configured to analyze received diagnoses and/or procedures in view of documents in the record using a natural language processor and a tiered information model to identify clinical indicators, and optionally markers. The identified information is compared with the received data for use in generating queries requesting evidence in support of the received diagnosis or procedure, or for use in validating the received information.

Methods, systems and computer program products for resolving multiple magnitudes assigned to a target vector are disclosed. A target vector that includes one or more target vector dimensions is received. One of the target vector dimensions is processed to determine a total number of magnitudes assigned to the processed target vector dimension. Also, a source vector that includes one or more source vector dimensions is received. The received source vector is processed to determine a total number of features associated with the source vector. When it is detected that the total number of magnitudes assigned to the processed target vector dimension exceeds one, one of the assigned magnitudes is selected based on one of the determined features associated with the source vector.

A-Life Medical | Date: 2016-06-22

Patient lifting frame for lifting and supporting an invalid patient. The lifting frame comprises two suspension side bars (1) each connectable at an upper end to a spreader bar and at a lower end to a pivotal suspension mounting (4) comprising a 2-axis connector (4A) supporting a cantilever side bar assembly (4B) of the lifting frame, and having a first pivotal axis and a second rotary axis transverse top the said first axis. Each cantilever side bar assembly (4B) is movable about the said rotary axis and has a first cantilever portion on one side of its 2-axis pivotal/rotary connector and a second cantilever portion on the other side thereof. The first cantilever portions mount patient underarm support elements (13) for engaging beneath the armpits of a patient, which carry side pad assemblies (15, 16) for engaging against opposite sides of a patients ribcage so that the underarm support elements (13) and side pad assemblies (15,16) form a patient upper body support means (13, 15, 16).

A-Life Medical | Date: 2014-05-07

Techniques for implementing Quality Assurance of the process of coding medical documents are disclosed. An audit of a coding process for a medical document is initiated by selecting and setting audit parameters. Using the selected parameters, a sample batch of coded documents is obtained from a universe of coded documents. The sample batch of coded documents is presented to auditor(s), and the auditor(s) provide corrections, which are recorded, and a score for each correction is calculated. A sample score, based on the corrections, is calculated in a manner that tracks to subjective auditor assessments of the process quality as being acceptable, marginally acceptable, or unacceptable, and which sample score accounts for the individual auditor subjectivity and an error.

A method, system and a computer program product for an automated interpretation and/or translation are disclosed. An automated interpretation and/or translation occurs by receiving language-based content from a user. The received language-based content is processed to interpret and/or translate the received language-based content into a target language. Also, a presence of a cultural sensitivity in the received language-based content is detected. Further, an appropriate guidance for dealing with the detected cultural sensitivity is provided.

A-Life Medical | Date: 2015-05-15

Methods, systems and computer program products for implementing a mere-parser are disclosed. Text data is processed to generate one or more parse items. A boundary based attribute associated with one of the parse items is identified, and the identified mere attribute is associated with one or more of the remaining parse items that is not blocked from associated with the boundary based attribute.

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