Hemophilia B in a female with intellectual disability caused by a deletion of Xq26.3q28 encompassing the F9

Background: Hemophilia B is an X-linked recessive disorder caused by mutations in the F9 on Xq27.1. Mainly males are affected but about 20% of female carriers have clotting factor IX activity below 0.40 IU/ml and bleeding problems. Fragile-X syndrome (FMR1) and FRAXE syndrome (AFF2) are well-known causes of X-linked recessive intellectual disability. Simultaneous deletion of both FMR1 and AFF2 in males results in severe intellectual disability. In females the phenotype is more variable. We report a 19-year-old female with severe intellectual disability and a long-standing bleeding history. Methods: A SNP array analysis (Illumina Human Cyto 12-SNP genotyping array) and sequencing of F9 were performed. Laboratory tests were performed to evaluate the bleeding diathesis. Results: Our patient was diagnosed with mild hemophilia B after finding an 11 Mb deletion of Xq26.3q28 that included the following genes among others IDS, SOX3, FMR1, AFF2, and F9. Conclusion: The case history demonstrates that a severe bleeding tendency suggestive of a hemostasis defect in patients with intellectual disability warrants careful hematological and genetic work-up even in the absence of a positive family history

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling.

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications

Antithrombotic therapy in patients undergoing TAVI: An overview of Dutch hospitals

Purpose To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI). Methods For every Dutch hospital performing TAVI (n =14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI. Results The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over twothirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively. Conclusions Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): Study protocol for a randomized controlled trial

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. Methods: The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. Discussion: The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Descubrimiento de proximidad asistido por la red, autenticación y establecimiento de enlace entre dispositivos móviles de comunicación en LTE 3GPP

La invención permite que un dispositivo descubra uno o más otros dispositivos dentro del rango para un modo de comunicación de dispositivo a dispositivo. Este descubrimiento de proximidad puede activar un dispositivo objetivo, p. Para comenzar a escuchar señales desde un dispositivo fuente o realizar cualquier otra acción basada en el descubrimiento de proximidad, como p. Cargando en una puerta de peaje. Un dispositivo fuente que desea descubrir transmite un mensaje que incluye un identificador o una representación del identificador. Este identificador puede ser un identificador del dispositivo de destino que se contactará o del dispositivo de origen o una derivación del mismo o una asociación de seguridad común utilizada por un conjunto de pares. El dispositivo objetivo compara el identificador de transmisión con un identificador conocido para establecer el descubrimiento de proximidad. (Traducción automática con Google Translate, sin valor legal

Descubrimiento de proximidad, autenticación y establecimiento de enlace entre dispositivos móviles de comunicación en LTE 3GPP

Un método para el descubrimiento de proximidad entre un dispositivo origen (1) y uno o más dispositivos objetivo (2) en donde el dispositivo origen (1) y el uno o más dispositivos objetivo (2) están configurados para conectarse en comunicación a una red, comprendiendo dicho método los pasos de: recibir (101) en el dispositivo origen (1) desde un servidor (3) en la red unos primeros datos (11) que comprenden un identificador (12), en donde el identificador (12) es un identificador temporal de difusión que identifica de forma unívoca al dispositivo origen (1); recibir (102) en el dispositivo objetivo (2) desde el servidor (3) unos segundos datos (20) que comprenden una primera representación (21) del identificador (12) del dispositivo origen (1) con el fin de permitir que el dispositivo objetivo (2) asocie el identificador (12) al dispositivo origen (1); difundir (103) por parte del dispositivo origen (1) una señal (30) que comprende una segunda representación del identificador (31) del dispositivo origen (1); recibir (104) en el dispositivo objetivo (2) la señal (30); y comparar (105) en el dispositivo objetivo la primera representación (21) del identificador (12) con la segunda representación (31) del identificador (12) para obtener un resultado de la comparación con el fin de establecer un descubrimiento de proximidad exitoso

Network-assisted proximity discovery, authentication and link establishment between communication mobile devices in 3GPP LTE

The invention enables a device to discover one or more other devices within range for a device-to-device mode of communication. This proximity discovery may trigger a target device, e.g. to start listening to signals from a source device or perform any other action based on the proximity discovery like e.g. charging at a toll gate. A source device that wants to be discovered broadcasts a message including an identifier or a representation of the identifier. This identifier may be an identifier of the target device to be contacted or of the source device or a derivation thereof or a common security association used by a set of peers. The target device compares the broadcast identifier with a known identifier to establish proximity discovery

Proximity Discovery, Authentication and Link Establishment Between Mobile Devices in 3GPP LTE

The invention enables a device to discover one or more other devices within range for a device-to-device mode of communication. This proximity discovery may trigger a target device, e.g. to start listening to signals from a source device or perform any other action based on the proximity discovery like e.g. charging at a toll gate. A source device that wants to be discovered broadcasts a message including an identifier or a representation of the identifier. This identifier may be an identifier of the target device to be contacted or of the source device or a derivation thereof or a common security association used by a set of peers. The target device compares the broadcast identifier with a known identifier to establish proximity discovery