Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation

A 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found in association with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with a fenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty: Advanced.)

Precipitable Water Variability Using SSM/I and GOES VAS Pathfinder Data Sets

Determining moisture variability for all weather scenes is critical to understanding the earth's hydrologic cycle and global climate changes. Remote sensing from geostationary satellites provides the necessary temporal and spatial resolutions necessary for global change studies. Due to antenna size constraints imposed with the use of microwave radiometers, geostationary satellites have carried instruments passively measuring radiation at infrared wavelengths or shorter. The shortfall of using infrared instruments in moisture studies lies in its inability to sense terrestrial radiation through clouds. Microwave emissions, on the other hand, are mostly unaffected by cloudy atmospheres. Land surface emissivity at microwave frequencies exhibit both high temporal and spatial variability thus confining moisture retrievals at microwave frequencies to over marine atmospheres (a near uniform cold background). This study intercompares the total column integrated water content Precipitable Water, (PW) as derived from both the Special Sensor Microwave Imager (SSM/I) and the Geostationary Operational Environmental Satellite (GOES) VISSR Atmospheric Sounder (VAS) pathfinder data sets. PW is a bulk parameter often used to quantify moisture variability and is important to understanding the earth's hydrologic cycle and climate system. This research has been spawned in an effort to combine two different algorithms which together can lead to a more comprehensive quantification of global water vapor. The approach taken here is to intercompare two independent PW retrieval algorithms and to validate the resultant retrievals against an existing data set, namely the European Center for Medium range Weather Forecasts (ECMWF) model analysis data

Cooperative Origin of Low-Density Domains in Liquid Water

We study the size of clusters formed by water molecules possessing large enough tetrahedrality with respect to their nearest neighbors. Using Monte Carlo simulation of the SPC/E model of water, together with a geometric analysis based on Voronoi tessellation, we find that regions of lower density than the bulk are formed by accretion of molecules into clusters exceeding a minimum size. Clusters are predominantly linear objects and become less compact as they grow until they reach a size beyond which further accretion is not accompanied by a density decrease. The results suggest that the formation of "ice-like" regions in liquid water is cooperative.Comment: 16 pages, 6 figure

Altered high-energy phosphate and membrane metabolism in Pelizaeus-Merzbacher disease using phosphorus magnetic resonance spectroscopy

Pelizaeus-Merzbacher disease is an X-linked recessive leucodystrophy of the central nervous system caused by mutations affecting the major myelin protein, proteolipid protein 1. The extent of the altered in vivo neurochemistry of protein, proteolipid protein 1 duplications, the most common form of Pelizaeus-Merzbacher disease, is, however, poorly understood. Phosphorus magnetic resonance spectroscopy is the only in vivo technique that can assess the biochemistry associated with high-energy phosphate and membrane phospholipid metabolism across different cortical, subcortical and white matter areas. In this cross-sectional study, whole-brain, multi-voxel phosphorus magnetic resonance spectroscopy was acquired at 3 T on 14 patients with Pelizaeus-Merzbacher disease with protein, proteolipid protein 1 duplications and 23 healthy controls (all males). Anabolic and catabolic levels of membrane phospholipids (phosphocholine and phosphoethanolamine, and glycerophosphoethanolamine and glycerophosphocholine, respectively), as well as phosphocreatine, inorganic orthophosphate and adenosine triphosphate levels relative to the total phosphorus magnetic resonance spectroscopy signal from 12 different cortical and subcortical areas were compared between the two groups. Independent of brain area, phosphocholine, glycerophosphoethanolamine and inorganic orthophosphate levels were significantly lower (P = 0.0025, P \u3c 0.0001 and P = 0.0002) and phosphocreatine levels were significantly higher (P \u3c 0.0001) in Pelizaeus-Merzbacher disease patients compared with controls. Additionally, there was a significant group-by-brain area interaction for phosphocreatine with post-hoc analyses demonstrating significantly higher phosphocreatine levels in patients with Pelizaeus-Merzbacher disease compared with controls across multiple brain areas (anterior and posterior white matter, superior parietal lobe, posterior cingulate cortex, hippocampus, occipital cortex, striatum and thalamus; all P ≤ 0.0042). Phosphoethanolamine, glycerophosphoethanolamine and adenosine triphosphate levels were not significantly different between groups. For the first-time, widespread alterations in phosphorus magnetic resonance spectroscopy metabolite levels of Pelizaeus-Merzbacher disease patients are being reported. Specifically, increased high-energy phosphate storage levels of phosphocreatine concomitant with decreased inorganic orthophosphate across multiple areas suggest a widespread reduction in the high-energy phosphate utilization in Pelizaeus-Merzbacher disease, and the membrane phospholipid metabolite deficits suggest a widespread degradation in the neuropil content/maintenance of patients with Pelizaeus-Merzbacher disease which includes axons, dendrites and astrocytes within cortex and the myelin microstructure and oligodendrocytes within white matter. These results provide greater insight into the neuropathology of Pelizaeus-Merzbacher disease both in terms of energy expenditure and membrane phospholipid metabolites. Future longitudinal studies are warranted to investigate the utility of phosphorus magnetic resonance spectroscopy as surrogate biomarkers in monitoring treatment intervention for Pelizaeus-Merzbacher disease

Unimodality Problems in Ehrhart Theory

Ehrhart theory is the study of sequences recording the number of integer points in non-negative integral dilates of rational polytopes. For a given lattice polytope, this sequence is encoded in a finite vector called the Ehrhart $h^*$-vector. Ehrhart $h^*$-vectors have connections to many areas of mathematics, including commutative algebra and enumerative combinatorics. In this survey we discuss what is known about unimodality for Ehrhart $h^*$-vectors and highlight open questions and problems.Comment: Published in Recent Trends in Combinatorics, Beveridge, A., et al. (eds), Springer, 2016, pp 687-711, doi 10.1007/978-3-319-24298-9_27. This version updated October 2017 to correct an error in the original versio

Placing a Price on Medical Device Innovation: The Example of Total Knee Arthroplasty

Background: Total knee arthroplasty (TKA) is common, effective, and cost-effective. Innovative implants promising reduced long-term failure at increased cost are under continual development. We sought to define the implant cost and performance thresholds under which innovative TKA implants are cost-effective. Methods: We performed a cost-effectiveness analysis using a validated, published computer simulation model of knee osteoarthritis. Model inputs were derived using published literature, Medicare claims, and National Health and Nutrition Examination Survey data. We compared projected TKA implant survival, quality-adjusted life expectancy (QALE), lifetime costs, and cost-effectiveness (incremental cost-effectiveness ratios or ICERs) of standard versus innovative TKA implants. We assumed innovative implants offered 5–70% decreased long-term TKA failure rates at costs 20–400% increased above standard implants. We examined the impact of patient age, comorbidity, and potential increases in short-term failure on innovative implant cost-effectiveness. Results: Implants offering ≥50% decrease in long-term TKA failure at ≤50% increased cost offered ICERs <$100,000 regardless of age or baseline comorbidity. An implant offering a 20$150,000 per QALY gained only among healthy 50–59-year-olds. Increasing short-term failure, consistent with recent device failures, reduced cost-effectiveness across all groups. Increasing the baseline likelihood of long-term TKA failure among younger, healthier and more active individuals further enhanced innovative implant cost-effectiveness among younger patients. Conclusions: Innovative implants must decrease actual TKA failure, not just radiographic wear, by 50–55% or more over standard implants to be broadly cost-effective. Comorbidity and remaining life span significantly affect innovative implant cost-effectiveness and should be considered in the development, approval and implementation of novel technologies, particularly in orthopedics. Model-based evaluations such as this offer valuable, unique insights for evaluating technological innovation in medical devices

IMECE2005-81300 EVALUATION OF HEAVY TRUCK ROLLOVER CRASHWORTHINESS

ABSTRACT Heavy trucks (those having a gross vehicle weight rating of greater than 10,000 pounds) are an essential part of the United States economy and account for 4% of all registered vehicles. The large size and weight of these vehicles can pose a serious safety threat to the vehicle&apos;s occupants in the event of a rollover collision. The rollover crashworthiness of heavy trucks, in particular the structural integrity of the cab, is analyzed in this paper. An actual rollover accident was analyzed and the cab design of an exemplar vehicle was evaluated. Modifications were made to the exemplar and an inverted drop test onto the roof of the cab was conducted. Recommendations for improving the rollover crashworthiness of heavy trucks are provided. An analysis of heavy truck rollover accidents was also conducted for data available from 1994-2002 by submitting queries to the Fatality Analysis Reporting System (FARS), which is administered by the National Highway Safety Administration (NHTSA), in order to determine the number of incapacitating and fatal injuries that occurred when the occupants were contained in the cab during a rollover accident. The percentage of incapacitating and fatal injuries for restrained occupants was determined by analyzing the rollover data obtained from the FARS rollover query that was used and was found to be 35%. Therefore, restrained occupants in heavy trucks can sustain significant injuries during rollover accidents, in part, due to insufficient rollover crashworthiness

Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design

BACKGROUND: Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. METHODS: This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. CONCLUSIONS: Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. TRIAL REGISTRATION: NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT0114977

A Transect Through the Pre-Silurian Rocks of Central Vermont; The Lincoln Massic and Its Immediate Cover; The Pre-Silurian Hinterland Along the Valleys of the White and Mad Rivers, Central Vermont; Metamorphism of Pre-Silurian Rocks, Central Vermont; Regional Geochemical Variations in Greenstones from the Central Vermont Appalachians

Guidebook for field trips in Vermont: New England Intercollegiate Geological Conference, 79th annual meeting, October 16, 17 and 18, 1987: Trips B-8; C-