Effect of the Butyrate Prodrug Pivaloyloxymethyl Butyrate (AN9) on a Mouse Model for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice. In conclusion, BA prodrugs like AN9 have ameliorative effects on SMNΔ7 SMA mice

Late erosion of a prophylactic Celect IVC filter into the aorta, right renal artery, and duodenal wall

We present the case of a patient with retrievable inferior vena cava (IVC) filter-related pseudoaneurysms of the infrarenal aorta and right renal artery, with associated erosion into the duodenal wall. The patient was seen 10 months following multiorgan trauma and placement of a prophylactic retrievable IVC filter (R-IVCF). Management required autogenous aortic reconstruction, caval repair, and subsequent right nephrectomy. This case demonstrates that R-IVCFs may be associated with significant risks, which is concerning, as a majority of prophylactic R-IVCFs placed after multisystem trauma are not removed

Augmenting Parametric Optimal Ascent Trajectory Modeling with Graph Theory

It has been well documented that decisions made in the early stages of Conceptual and Pre-Conceptual design commit up to 80% of total Life-Cycle Cost (LCC) while engineers know the least about the product they are designing [1]. Once within Preliminary and Detailed design however, making changes to the design becomes far more difficult to enact in both cost and schedule. Primarily this has been due to a lack of detailed data usually uncovered later during the Preliminary and Detailed design phases. In our current budget-constrained environment, making decisions within Conceptual and Pre-Conceptual design which minimize LCC while meeting requirements is paramount to a program's success. Within the arena of launch vehicle design, optimizing the ascent trajectory is critical for minimizing the costs present within such concerns as propellant, aerodynamic, aeroheating, and acceleration loads while meeting requirements such as payload delivered to a desired orbit. In order to optimize the vehicle design its constraints and requirements must be known, however as the design cycle proceeds it is all but inevitable that the conditions will change. Upon that change, the previously optimized trajectory may no longer be optimal, or meet design requirements. The current paradigm for adjusting to these updates is generating point solutions for every change in the design's requirements [2]. This can be a tedious, time-consuming task as changes in virtually any piece of a launch vehicle's design can have a disproportionately large effect on the ascent trajectory, as the solution space of the trajectory optimization problem is both non-linear and multimodal [3]. In addition, an industry standard tool, Program to Optimize Simulated Trajectories (POST), requires an expert analyst to produce simulated trajectories that are feasible and optimal [4]. In a previous publication the authors presented a method for combatting these challenges [5]. In order to bring more detailed information into Conceptual and Pre-Conceptual design, knowledge of the effects originating from changes to the vehicle must be calculated. In order to do this, a model capable of quantitatively describing any vehicle within the entire design space under consideration must be constructed. This model must be based upon analysis of acceptable fidelity, which in this work comes from POST. Design space interrogation can be achieved with surrogate modeling, a parametric, polynomial equation representing a tool. A surrogate model must be informed by data from the tool with enough points to represent the solution space for the chosen number of variables with an acceptable level of error. Therefore, Design Of Experiments (DOE) is used to select points within the design space to maximize information gained on the design space while minimizing number of data points required. To represent a design space with a non-trivial number of variable parameters the number of points required still represent an amount of work which would take an inordinate amount of time via the current paradigm of manual analysis, and so an automated method was developed. The best practices of expert trajectory analysts working within NASA Marshall's Advanced Concepts Office (ACO) were implemented within a tool called multiPOST. These practices include how to use the output data from a previous run of POST to inform the next, determining whether a trajectory solution is feasible from a real-world perspective, and how to handle program execution errors. The tool was then augmented with multiprocessing capability to enable analysis on multiple trajectories simultaneously, allowing throughput to scale with available computational resources. In this update to the previous work the authors discuss issues with the method and solutions

Gene transfection of HEK cells on supermacroporous polyacrylamide monoliths: a comparison of transient and stable recombinant protein expression in perfusion culture

Transient and continuous recombinant protein expression by HEK cells was evaluated in a perfused monolithic bioreactor. Highly porous synthetic cryogel scaffolds (10ml bed volume) were characterised by scanning electron microscopy and tested as cell substrates. Efficient seeding was achieved (94% inoculum retained, with 91-95% viability). Metabolite monitoring indicated continuous cell growth, and endpoint cell density was estimated by genomic DNA quantification to be 5.2x108, 1.1x109 and 3.5x1010 at day 10, 14 and 18. Culture of stably transfected cells allowed continuous production of the Drosophila cytokine Spätzle by the bioreactor at the same rate as in monolayer culture (total 1.2 mg at d18) and this protein was active. In transient transfection experiments more protein was produced per cell compared with monolayer culture. Confocal microscopy confirmed homogenous GFP expression after transient transfection within the bioreactor. Monolithic bioreactors are thus shown to be a flexible and powerful tool for manufacturing recombinant proteins

Influence of computed tomography angiography reconstruction software on anatomic measurements and endograft component selection for endovascular abdominal aortic aneurysm repair

ObjectiveThree-dimensional (3D) centerline reconstruction of computed tomography angiography (CTA) images permits detailed anatomic characterization of abdominal aortic aneurysms and facilitates planning of endovascular repair. Although several programs for 3D CTA reconstruction and measurement are available, direct comparisons have not been published, and reliability between software platforms has not been characterized. We evaluated agreement between anatomic measurements obtained from 3D CTA reconstructions using three commercially available software programs and characterized concordance between the programs for endograft component selection.MethodsImages from 92 CTA studies performed before abdominal aortic aneurysm repair were reconstructed and measured using three different software programs: independent reconstruction with proprietary software (Preview; M2S Inc, Lebanon, NH), surgeon-based reconstruction with proprietary software (AquariusNet Thin Client; TeraRecon Inc, San Mateo, Calif), and surgeon-based reconstruction with open-source software (Osirix MD; Pixmeo, Geneva, Switzerland). Agreement between outer wall diameter and length measurements obtained from centerline reconstructions created with each program was evaluated using scatter plots, intraclass correlation coefficients, and Bland-Altman plots. Concordance between aortic and iliac endograft component diameters selected from measurements with each program based on published instructions for use was examined using weighted κ statistics.ResultsDiameter measurements were generally similar between programs. Mean diameters at all locations were within ≤1 mm of one another, and mean length measurements were within ≤10 mm of one another for all pairwise comparisons. Intraclass correlations coefficients between programs for diameter measurements were comparable between programs (≥0.82 for all diameter comparisons and ≥0.88 for all length comparisons) and indicated good correlation. Pair-wise comparisons indicated similar rates of identical and adjacent size endograft component selection without an obvious trend toward superior agreement for any two programs. Rates of identical proximal endograft diameter selection ranged from 46% to 59%, whereas 89% to 100% of proximal endograft diameters selected between programs were within one adjacent (smaller or larger) size of each other. For iliac endograft selection, rates of identical component diameter selection between programs ranged from 36% to 69%, and 58% to 99% of selected iliac endograft diameters were within one adjacent size.ConclusionsOuter wall diameter and centerline length measurements obtained from 3D CTA reconstructions demonstrated good correlation between imaging analysis software programs, and graft diameter selections based on these measurements were reasonably similar. Comparable 3D CTA reconstruction measurements can be generated from independent and surgeon-based approaches using proprietary and open-source software, and the selection of a method to interpret images for endograft planning can be individualized according to operator experience and available resources while retaining sufficient accuracy

Multiple aneurysms in childhood

AbstractArterial aneurysms in children are rare. When present, they are often associated with connective tissue disorders or arteritidies. Idiopathic aneurysms occurring at multiple sites throughout the arterial tree are rare, with only ten cases reported. This report describes a case of multiple arterial aneurysms of uncertain origin involving upper-extremity, extracranial cerebrovascular, aortoiliac, and renal arteries in a 14-year-old boy. The clinical presentation, vascular reconstruction, pathologic findings, and a brief review of the literature are described

Modelling multiscale aspects of colorectal cancer

Colorectal cancer (CRC) is responsible for nearly half a million deaths annually world-wide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network. We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole

Cottonwood Creek Preliminary Assessment

Cottonwood Creek is located in Powell County, Montana and flows through the town of Deer Lodge. The Natural Resource Conservation Service (NRCS), will be working with ranch owners along Cottonwood Creek on restoration and conservation projects in the spring of 2001. In September and October of 2000, six graduate students from the University of Montana completed a baseline assessment of the lower Cottonwood Creek watershed, including the tributary Reese Anderson Creek. The assessment is the start of a more comprehensive assessment to be completed in the summer of 2001. The purpose of this baseline assessment is to characterize the current condition of Cottonwood Creek. The objectives of this study include: 1. To assess the current condition (“health”) of Cottonwood Creek’s riparian areas. 2. To provide baseline data needed to evaluate the benefits of conservation and restoration projects. 3. To gather information about the current and historical land-uses in the Cottonwood Creek Watershed. 4. To make recommendations on a landowner monitoring system. Study Approach The Fall 200 study synthesized existing data and conducted new field observations. Existing data includes maps, soil information, geology, climate, and historically and current land uses. The major component of the field research was the evaluation of the riparian corridor using University of Montana’s Riparian and Wetland Research Program’s (RWRP) Lotic Assessment Form. This method breaks up the riparian corridor into about ¼ mile to ¾ mile sections, called polygons, and evaluates each polygon’s vegetation, stream bank stability, and invasive species. Each polygon is then rated as “Properly Functioning”, “Functioning but at Risk”, or “Nonfunctioning”. Other field data collected included measurement of the stream cross section, photo documentation of the riparian area, and stream discharge. Summary of results The Fall 2000 assessment broke Cottonwood Creek into 11 polygons and Reese Anderson Creek into 4 polygons. The RWRP Lotic Health Assessment scored five polygons as Functioning but at Risk, and the remaining ten polygons, including all 4 on Reese Anderson Creek, were found to be Non-Functioning systems. A big factor in reduced functioning along Cottonwood Creek is over grazing which resulted in a streambank instability and lack of woody vegetation. This is most evident on Reese Anderson Creek and the downstream portion of Cottonwood Creek. Other concerns in the riparian corridor included dewatering, use of rip-rap and invasive species. Comparing the cross sections measurements made in each polygon showed a widening trend downstream. A likely cause for this trend is the lack of woody vegetation along the stream bank downstream. Also, the limited discharged data collected suggested that the stream loses water as it flows downstream. This is likely because of the amount of diversions along the stream. However, further measurements need to be taken in the spring of 2001 to gain a better understanding of how much of a loss there is

Magazine and reader constructions of 'metrosexuality' and masculinity: a membership categorisation analysis

Since the launch of men's lifestyle magazines in the 1980s, academic literature has predominantly focused on them as a cultural phenomenon arising from entrepreneurial and commercial initiatives and/or as cultural texts that proffer representations of masculinity such as 'new lad' and 'new dad'. This paper steps aside from the focus on culture and, instead, treats magazine content as a discursive space in which gender and sexuality are oriented to, negotiated, and accomplished within and beyond the magazine itself (i.e. through readers' responses). Specifically, membership categorisation analysis is deployed to explore how the relatively new (and perhaps alternative) category for men - 'metrosexual' - is presented and received. Our analysis suggests that masculinity concerns are central in debates about 'metrosexuality', with self-identified 'metrosexuals' invoking heterosexual prowess and self-respect on the one hand, and critics (e.g. selfidentified 'real men') lamenting 'metrosexuality' for its perceived effeminacy and lack of authenticity on the other. Implications for understanding contemporary masculinities are discussed

Substructure in the Coma Cluster: Giants vs Dwarfs

The processes that form and shape galaxy clusters, such as infall, mergers and dynamical relaxation, tend to generate distinguishable differences between the distributions of a cluster's giant and dwarf galaxies. Thus the dynamics of dwarf galaxies in a cluster can provide valuable insights into its dynamical history. With this in mind, we look for differences between the spatial and velocity distributions of giant (b18) galaxies in the Coma cluster. Our redshift sample contains new measurements from the 2dF and WYFFOS spectrographs, making it more complete at faint magnitudes than any previously studied sample of Coma galaxies. It includes 745 cluster members - 452 giants and 293 dwarfs. We find that the line-of-sight velocity distribution of the giants is significantly non-Gaussian, but not that for the dwarfs. A battery of statistical tests of both the spatial and localised velocity distributions of the galaxies in our sample finds no strong evidence for differences between the giant and dwarf populations. These results rule out the cluster as a whole having moved significantly towards equipartition, and they are consistent with the cluster having formed via mergers between dynamically-relaxed subclusters.Comment: 23 pages, 6 figures, to appear in Ap