Implant compositions for the unidirectional delivery of therapeutic compounds to the brain

The present invention provides, in some aspects, bilayered and trilayered pharmaceutical implant compositions for the unidirectional delivery of anti-cancer compounds to the brain over a period of time (e.g., several weeks, 1, 2, 3, 4, 5, 6, 7 days, or 1, 2, 3, weeks, or any range derivable therein) following the removal of glioblastoma multiforme or other malignant tumors in the brain.Board of Regents, University of Texas Syste

Athletes and Arrhythmias

Sudden cardiac death related to athletic competition is a rare but tragic event. The victims are typically young with no previous cardiovascular symptoms or limitations. The majority of sudden cardiac death events in athletes are due to ventricular arrhythmias as a result of underlying molecular and/or structural level pathologic substrate. In this article, we will review the physiologic cardiac adaptations to exercise along with arrhythmias seen in athletes with a focus on those commonly associated with sudden cardiac death

Design of a Direct-Detection Wind and Aerosol Lidar for Mars Orbit

The present knowledge of the Mars atmosphere is greatly limited by a lack of global measurements of winds and aerosols. Hence, measurements of height-resolved wind and aerosol profiles are a priority for new Mars orbiting missions. We have designed a direct-detection lidar (MARLI) to provide global measurements of dust, winds and water ice profiles from Mars orbit. From a 400-km polar orbit, the instrument is designed to provide wind and backscatter measurements with a vertical resolution of 2 km and with resolution of 2 in latitude along track. The instrument uses a single-frequency, seeded Nd:YAG laser that emits 4 mJ pulses at 1064 nm at a 250 Hz pulse rate. The receiver utilizes a 50-cm diameter telescope and a double edge Fabry-Prot etalon as a frequency discriminator to measure the Doppler shift of the aerosol-backscatter profiles. The receiver also includes a polarization-sensitive channel to detect the cross-polarized backscatter profiles from water ice. The receiver uses a sensitive 4 4 pixel HgCdTe avalanche photodiode array as a detector for all signals. Here we describe the measurement concept, instrument design, and calculate its performance for several cases of Mars atmospheric conditions. The calculations show that under a range of atmospheric conditions MARLI is capable of measuring wind speed profiles with random error of 24 m/s within the first three scale heights, enabling vertically resolved mapping of transport processes in this important region of the atmosphere

Spontaneous coordinated activity in cultured networks: analysis of multiple ignition sites, primary circuits, and burst phase delay distributions

This article discusses an analysis of multiple ignition sites, primary circuits, and burst phase delay distributions

Cue-Dependent Inhibition in Posttraumatic Stress Disorder and Attention- Deficit/Hyperactivity Disorder

Objective Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are common among military veterans, but the comorbidity of these two psychiatric disorders remains largely unstudied. Evaluating response inhibition and cue-dependent learning as behavioral and neurocognitive mechanisms underlying ADHD/PTSD can inform etiological models and development of tailored interventions. Method A cued go/no-go task evaluated response inhibition in 160 adult males. Participants were recruited from the community and a Veterans Administration medical center. Four diagnostic groups were identified: ADHD-only, PTSD-only, ADHD + PTSD, controls. Results Group differences were observed across most indices of inhibitory functioning, reaction time, and reaction time variability, whereby PTSD-only and ADHD + PTSD participants demonstrated deficits relative to controls. No cue dependency effects were observed. Conclusion Finding complement prior work on neurocognitive mechanisms underlying ADHD, PTSD, and ADHD + PTSD. Lack of expected group differences for the ADHD-only group may be due to limited power. Additional work is needed to better characterize distinctions among clinical groups, as well as to test effects among women and youth

Predicting the costs of managing patients with chronic obstructive pulmonary disease

SummaryThe economic consequences of chronic obstructive pulmonary disease (COPD) are considerable, although the factors that best predict costs are largely unknown. This study used a population-based cohort to identify the clinical factors during an index year that were most predictive of increased direct medical costs in the subsequent year, and to develop a predictive model that described the cost variations in COPD.The medical records of 2116 patients enrolled in one regional health system who had COPD and healthcare resource utilisation data for 1998 and 1999, were abstracted for information about symptoms, smoking history, chronic illnesses, and pulmonary function data. All inpatient, outpatient and pharmacy utilisation data for each subject for 1999 were extracted from the database. Total costs for each individual were transformed to a log scale. Potential causes of cost variability (predictor variables) were defined and classified into sets (or domains). Multiple linear regression models were fitted for each domain.The study demonstrated that severity of airflow obstruction, as assessed by FEV1% predicted, is a significant but weak predictor of future healthcare resource utilisation—prior hospitalisation and home oxygen use, the presence of comorbid conditions and symptoms of dyspnoea are better predictors of costs. Those interested in the economic benefits of new COPD treatments and disease management programs need to carefully account for these factors

Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study.

Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease

Plate Boundary Observatory and related networks: GPS data analysis methods and geodetic products

The Geodesy Advancing Geosciences and EarthScope (GAGE) Facility Global Positioning System (GPS) Data Analysis Centers produce position time series, velocities, and other parameters for approximately 2000 continuously operating GPS receivers spanning a quadrant of Earth’s surface encompassing the high Arctic, North America, and Caribbean. The purpose of this review is to document the methodology for generating station positions and their evolution over time and to describe the requisite trade-offs involved with combination of results. GAGE GPS analysis involves formal merging within a Kalman filter of two independent, loosely constrained solutions: one is based on precise point positioning produced with the GIPSY/OASIS software at Central Washington University and the other is a network solution based on phase and range double-differencing produced with the GAMIT software at New Mexico Institute of Mining and Technology. The primary products generated are the position time series that show motions relative to a North America reference frame and secular motions of the stations represented in the velocity field. The position time series themselves contain a multitude of signals in addition to the secular motions. Coseismic and postseismic signals, seasonal signals from hydrology, and transient events, some understood and others not yet fully explained, are all evident in the time series and ready for further analysis and interpretation. We explore the impact of analysis assumptions on the reference frame realization and on the final solutions, and we compare within the GAGE solutions and with others