Early Detection of Critical Pulmonary Shunts in Infants

This paper aims to improve the design of modern Medical Cyber Physical Systems through the addition of supplemental noninvasive monitors. Specifically, we focus on monitoring the arterial blood oxygen content (CaO2), one of the most closely observed vital signs in operating rooms, currently measured by a proxy - peripheral hemoglobin oxygen saturation (SpO2). While SpO2 is a good estimate of O2 content in the finger where it is measured, it is a delayed measure of its content in the arteries. In addition, it does not incorporate system dynamics and is a poor predictor of future CaO2 values. Therefore, as a first step towards supplementing the usage of SpO2, this work introduces a predictive monitor designed to provide early detection of critical drops in CaO2 caused by a pulmonary shunt in infants. To this end, we develop a formal model of the circulation of oxygen and carbon dioxide in the body, characterized by unknown patient-unique parameters. Employing the model, we design a matched subspace detector to provide a near constant false alarm rate invariant to these parameters and modeling uncertainties. Finally, we validate our approach on real-patient data from lung lobectomy surgeries performed at the Children\u27s Hospital of Philadelphia. Given 198 infants, the detector predicted 81% of the critical drops in CaO2 at an average of about 65 seconds earlier than the SpO2-based monitor, while achieving a 0:9% false alarm rate (representing about 2 false alarms per hour)

Use of the national low-temperature neutron irradiation facility for fusion materials research

The National Low-Temperature Neutron Irradiation Facility (NLTNIF), now constructed and currently being evaluated, will provide high radiation intensities and special environmental and testing conditions for qualified experiments at no cost to users. The NLTNIF will be of interest for both basic and applied research on fusion reactor materials. A general description and major specifications of the facility are presented along with recent results of the performance tests. In addition, a description is given of the procedure and experimental assemblies needed to perform experiments in the NLTNIF

Characterization of the National Low-Temperature Neutron Irradiation Facility

The National Low-Temperature Neutron Irradiation Facility (NLTNIF) is now operating at the Bulk Shielding Reactor at ORNL. The facility provides high radiation intensities and special environmental and testing conditions for qualified experiments at no cost to users. A general description and major specifications of the NLTNIF are presented along with the results of performance tests. In addition, the hardware and other considerations required to perform experiments in the NLTNIF are described

Inhibiting transthyretin conformational changes that lead to amyloid fibril formation

Insoluble protein fibrils resulting from the self-assembly of a conformational intermediate are implicated as the causative agent in several severe human amyloid diseases, including Alzheimer's disease, familial amyloid polyneuropathy, and senile systemic amyloidosis. The latter two diseases are associated with transthyretin (TTR) amyloid fibrils, which appear to form in the acidic partial denaturing environment of the lysosome. Here we demonstrate that flufenamic acid (Flu) inhibits the conformational changes of TTR associated with amyloid fibril formation. The crystal structure of TTR complexed with Flu demonstrates that Flu mediates intersubunit hydrophobic interactions and intersubunit hydrogen bonds that stabilize the normal tetrameric fold of TTR. A small-molecule inhibitor that stabilizes the normal conformation of a protein is desirable as a possible approach to treat amyloid diseases. Molecules such as Flu also provide the means to rigorously test the amyloid hypothesis, i.e., the apparent causative role of amyloid fibrils in amyloid disease

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

Validation of the disease burden morbidity assessment by self-report in a French-speaking population

<p>Abstract</p> <p>Background</p> <p>The Disease Burden Morbidity Assessment (DBMA) is a self-report questionnaire used to estimate the disease burden experienced by patients. The aim of this study was to test and to measure the properties of the French translation of the DBMA (DBMA-Fv).</p> <p>Methods</p> <p>The original version of the DBMA was translated into French (Canadian) and first assessed during cognitive interviews. In the validation study, patients recruited during consecutive consultation periods completed the DBMA-Fv questionnaire while they were in the waiting room of a primary care setting (T1). Participants completed the same questionnaire mailed to their home two weeks later (T2). Concomitant validity of the DBMA-Fv was assessed using the Cumulative Illness Rating Scale (CIRS). Patient medical records were reviewed to verify chronic diseases and past medical history.</p> <p>Results</p> <p>Ninety-seven patients were recruited and 85 (88%) returned the mailed questionnaires; 5 (5.9%) were incomplete. DBMA-Fv scores of the 80 participants with a complete questionnaire at T2 ranged from 0 to 30 (median 5.5, mean 7.7, SD = 7.0). Test-retest reliability of the DBMA-Fv was high (ICC: 0.86, 95% CI: 0.79-0.92). The DBMA-Fv and the CIRS correlated moderately at T1 (r = 0.46, 95% CI: 0.26 - 0.62, <it>p </it>< 0.01) and T2 (r = 0.56, 95% CI: 0.38 - 0.70, <it>p </it>< 0.01). The mean (SD) sensitivity of patient reports of a condition in relation to chart review at T2 was 73.9 (8.4) (range 62.5% to 90%). The overall mean (SD) specificity was 92.2 (6.7) (range 77.6% to 98.6%).</p> <p>Conclusions</p> <p>The DBMA-Fv's properties are similar to its English counterpart as to its median sensitivity and specificity compared to chart reviews. It correlated moderately with an established index of multimorbidity. A high percentage of patients were able to complete the test correctly as a mail questionnaire and it showed high test-retest reliability.</p

GLIDA: GPCR—ligand database for chemical genomics drug discovery—database and tools update

G-protein coupled receptors (GPCRs) represent one of the most important families of drug targets in pharmaceutical development. GLIDA is a public GPCR-related Chemical Genomics database that is primarily focused on the integration of information between GPCRs and their ligands. It provides interaction data between GPCRs and their ligands, along with chemical information on the ligands, as well as biological information regarding GPCRs. These data are connected with each other in a relational database, allowing users in the field of Chemical Genomics research to easily retrieve such information from either biological or chemical starting points. GLIDA includes a variety of similarity search functions for the GPCRs and for their ligands. Thus, GLIDA can provide correlation maps linking the searched homologous GPCRs (or ligands) with their ligands (or GPCRs). By analyzing the correlation patterns between GPCRs and ligands, we can gain more detailed knowledge about their conserved molecular recognition patterns and improve drug design efforts by focusing on inferred candidates for GPCR-specific drugs. This article provides a summary of the GLIDA database and user facilities, and describes recent improvements to database design, data contents, ligand classification programs, similarity search options and graphical interfaces. GLIDA is publicly available at http://pharminfo.pharm.kyoto-u.ac.jp/services/glida/. We hope that it will prove very useful for Chemical Genomics research and GPCR-related drug discovery