De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia

Item does not contain fulltex

Should the ultrasound probe replace your stethoscope? A SICS-I sub-study comparing lung ultrasound and pulmonary auscultation in the critically ill

BACKGROUND: In critically ill patients, auscultation might be challenging as dorsal lung fields are difficult to reach in supine-positioned patients, and the environment is often noisy. In recent years, clinicians have started to consider lung ultrasound as a useful diagnostic tool for a variety of pulmonary pathologies, including pulmonary edema. The aim of this study was to compare lung ultrasound and pulmonary auscultation for detecting pulmonary edema in critically ill patients. METHODS: This study was a planned sub-study of the Simple Intensive Care Studies-I, a single-center, prospective observational study. All acutely admitted patients who were 18 years and older with an expected ICU stay of at least 24 h were eligible for inclusion. All patients underwent clinical examination combined with lung ultrasound, conducted by researchers not involved in patient care. Clinical examination included auscultation of the bilateral regions for crepitations and rhonchi. Lung ultrasound was conducted according to the Bedside Lung Ultrasound in Emergency protocol. Pulmonary edema was defined as three or more B lines in at least two (bilateral) scan sites. An agreement was described by using the Cohen κ coefficient, sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy. Subgroup analysis were performed in patients who were not mechanically ventilated. RESULTS: The Simple Intensive Care Studies-I cohort included 1075 patients, of whom 926 (86%) were eligible for inclusion in this analysis. Three hundred seven of the 926 patients (33%) fulfilled the criteria for pulmonary edema on lung ultrasound. In 156 (51%) of these patients, auscultation was normal. A total of 302 patients (32%) had audible crepitations or rhonchi upon auscultation. From 130 patients with crepitations, 86 patients (66%) had pulmonary edema on lung ultrasound, and from 209 patients with rhonchi, 96 patients (46%) had pulmonary edema on lung ultrasound. The agreement between auscultation findings and lung ultrasound diagnosis was poor (κ statistic 0.25). Subgroup analysis showed that the diagnostic accuracy of auscultation was better in non-ventilated than in ventilated patients. CONCLUSION: The agreement between lung ultrasound and auscultation is poor

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening

Manufacturing flow line systems: a review of models and analytical results

The most important models and results of the manufacturing flow line literature are described. These include the major classes of models (asynchronous, synchronous, and continuous); the major features (blocking, processing times, failures and repairs); the major properties (conservation of flow, flow rate-idle time, reversibility, and others); and the relationships among different models. Exact and approximate methods for obtaining quantitative measures of performance are also reviewed. The exact methods are appropriate for small systems. The approximate methods, which are the only means available for large systems, are generally based on decomposition, and make use of the exact methods for small systems. Extensions are briefly discussed. Directions for future research are suggested.National Science Foundation (U.S.) (Grant DDM-8914277

Data-centric protection in DICOM

In this paper we address the problem of privacy protection and trust enhancement in a distributed healthcare eco system. Increased trust in other parties of the eco system encourages medical entities to share data. This increases the availability of data and consequently improves the general quality of health care. We present two different solutions to the above described problem, both being developed using the DICOM standard (Digital Imaging and Communications in Medicine). The first approach, which is partially relying on legislation, uses sticky policies and commitment protocols to enhance trust. We propose to attach the access control policies to the data in the DICOM files. Furthermore, the source of data disclosure makes sure that the destination commits to enforce the policies by obtaining a signature on the policies and thus providing a proof of the commitment by the destination. The second approach aims at increasing trust by technical enforcement. For this purpose, digital rights management (DRM) technology is used. We demonstrate that it is possible to create a DICOM DRM container using the tools provided by this standard, hence still guaranteeing backward compatibility

End-to-end security for personal telehealth

Personal telehealth is in rapid development with innovative emerging applications like disease management. With personal telehealth people participate in their own care supported by an open distributed system with health services. This poses new end-to-end security and privacy challenges. In this paper we introduce new end-to-end security requirements and present a design for consent management in the context of the Continua Health Alliance architecture. Thus, we empower patients to control how their health information is shared and used in a personal telehealth eco-system

Emergency access to protected health records

Digital Rights Management (DRM) schemes are receiving increased attention in the healthcare domain for the protection of sensitive health records as they offer security against insider attacks and advance protection features such as usage control. However, to be accepted by health care providers, a DRM solution has to fulfill specific healthcare requirements including emergency access. In this paper, we propose such DRM solution that can be deployed in highly distributed environments of electronic or personal health record infrastructures

eConsent management and enforcement in personal telehealth

Advances in information and communication technologies are expected to bring large benefits in the healthcare domain. Personal telehealth is one such example that has the potential to address some of the important challenges currently faced by healthcare such as improvement in the quality of healthcare delivery while at the same time reducing the cost. However concerns about information security and privacy are primary reasons for the lack of deployment of personal telehealth systems, besides problems with regard to safety and integration of multi-vendor systems. In this paper we present consent principles crucial to the privacy protection of individuals. Further, based on these principles, we describe consent management and enforcement functionality as outlined by the Continua Health Alliance and elaborate on how it can enable different usage scenarios with different trust levels and security requirements

Odour memory: How to test it? Incidental or intentional learning, implicit or explicit recognition

National audienc