Age- and Lesion-Related Comorbidity Burden Among US Adults With Congenital Heart Disease: A Population-Based Study.

Background As patients with congenital heart disease (CHD) are living longer, understanding the comorbidities they develop as they age is increasingly important. However, there are no published population-based estimates of the comorbidity burden among the US adult patients with CHD. Methods and Results Using the IBM MarketScan commercial claims database from 2010 to 2016, we identified adults aged ≥18 years with CHD and 2 full years of continuous enrollment. These were frequency matched with adults without CHD within categories jointly defined by age, sex, and dates of enrollment in the database. A total of 40 127 patients with CHD met the inclusion criteria (mean [SD] age, 36.8 [14.6] years; and 48.2% were women). Adults with CHD were nearly twice as likely to have any comorbidity than those without CHD (P<0.001). After adjusting for covariates, patients with CHD had a higher prevalence risk ratio for "previously recognized to be common in CHD" (risk ratio, 9.41; 95% CI, 7.99-11.1), "other cardiovascular" (risk ratio, 1.73; 95% CI, 1.66-1.80), and "noncardiovascular" (risk ratio, 1.47; 95% CI, 1.41-1.52) comorbidities. After adjusting for covariates and considering interaction with age, patients with severe CHD had higher risks of previously recognized to be common in CHD and lower risks of other cardiovascular comorbidities than age-stratified patients with nonsevere CHD. For noncardiovascular comorbidities, the risk was higher among patients with severe than nonsevere CHD before, but not after, the age of 40 years. Conclusions Our data underscore the unique clinical needs of adults with CHD compared with their peers. Clinicians caring for CHD may want to use a multidisciplinary approach, including building close collaborations with internists and specialists, to help provide appropriate care for the highly prevalent noncardiovascular comorbidities

Interplanetary Trajectory Design for NASA's Common Probe Study

The Galileo Probe, Pioneer-Venus probes, and SPRITE concept all share a number of common characteristics. They all follow a similar entry and descent sequence, using an aeroshell to protect against entry environments, and parachutes to aid in extrusion and descent speed control of the descent vehicle containing the science instruments. The descent vehicles all contained similar instruments (e.g. mass spectrometers and atmosphere structure sensors), and data was either relayed back to a carrier spacecraft (Galileo Probe, SPRITE) or transmitted direct to Earth (Pioneer-Venus). Based on these similar characteristics, NASA initiated a study to investigate a common probe' that might be designed to perform similar science in a variety of planetary environments. This concept would leverage a common aeroshell design, and descent vehicle designs that could be made as similar as possible (the primary exception being that Venus will require a pressure vessel due to the extreme pressures and temperatures seen in the lower portion of the descent). To support the Common Probe study, GSFC and JPL performed a series of interplanetary trajectory analyses to help develop the mission designs for Venus, Jupiter, Saturn, Uranus, and Neptune. Primary considerations in the trajectory modeling included: a maximum of 12-year time of flight (for outer planet destinations), generation of both steep and shallow entry trajectories to each destination (where steep and shallow resulted in approximately 150 g and 50 g peak deceleration during entry at each location), and consideration of the data relay. Gravity assists and trajectories with low delta-V requirements (typically much less than 500 m/s) were also incorporated into the design process to enable launch on existing vehicles such as the Atlas V

Government pension policy and the cost of labor and capital

This article examines how the pension insurance provided by the PBGC and the tax treatment of pension plans affect the cost of labor and capital. Two important aspects of the insurance program are (1) the premium schedule and (2) an employer's liability for unfunded pension benefits (the deductible). These two aspects interact to increase the cost of capital relative to labor, especially for firms with underfunded plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45413/1/10693_2004_Article_BF00119168.pd

Diffusion of Iodine and Rhenium in Category 3 Waste Encasement Concrete and Soil Fill Material

Assessing long-term performance of Category 3 waste cement grouts for radionuclide encasement requires knowledge of the radionuclide-cement interactions and mechanisms of retention (i.e. sorption or precipitation). This understanding will enable accurate prediction of radionuclide fate when the waste forms come in contact with groundwater. A set of diffusion experiments using carbonated and non-carbonated concrete-soil half cells was conducted under unsaturated conditions (4% and 7% by wt moisture content). Spiked concrete half-cell specimens were prepared with and without colloidal metallic iron addition and were carbonated using supercritical carbon dioxide. Spikes of I and Re were added to achieve measurable diffusion profile in the soil part of the half-cell. In addition, properties of concrete materials likely to influence radionuclide migration such as carbonation were evaluated in an effort to correlate these properties with the release of iodine and rhenium

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Maternal microchimerism in the livers of patients with Biliary atresia

BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2–4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1–142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA