Parental mosaicism in RYR1-related Central Core Disease.

Myopathies due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene are amongst the most common non-dystrophic neuromuscular disorders and have been associated with both dominant and recessive inheritance. Several cases with apparently de novo dominant inheritance have been reported. Here we report two siblings with features of Central Core Disease (CCD) born to unaffected parents. Genetic testing revealed a heterozygous dominant RYR1 c.14582G>A (p. Arg4861His) mutation previously identified in other CCD pedigrees. The variant was absent in blood from the asymptomatic mother but detected at low but variable levels in blood- and saliva-derived DNA from the unaffected father, suggesting that this mutation has arisen as a paternal post-zygotic de novo event. These findings suggest that parental mosaicism should be considered in RYR1-related myopathies, and may provide one possible explanation for the marked intergenerational variability seen in some RYR1 pedigrees.

Understanding Pen and Touch Interaction for Data Exploration on Interactive Whiteboards.

Current interfaces for common information visualizations such as bar graphs, line graphs, and scatterplots usually make use of the WIMP (Windows, Icons, Menus and a Pointer) interface paradigm with its frequently discussed problems of multiple levels of indirection via cascading menus, dialog boxes, and control panels. Recent advances in interface capabilities such as the availability of pen and touch interaction challenge us to re-think this and investigate more direct access to both the visualizations and the data they portray. We conducted a Wizard of Oz study to explore applying pen and touch interaction to the creation of information visualization interfaces on interactive whiteboards without implementing a plethora of recognizers. Our wizard acted as a robust and flexible pen and touch recognizer, giving participants maximum freedom in how they interacted with the system. Based on our qualitative analysis of the interactions our participants used, we discuss our insights about pen and touch interactions in the context of learnability and the interplay between pen and touch gestures. We conclude with suggestions for designing pen and touch enabled interactive visualization interfaces.

X-ray coherent scattering form factors of tissues, water and plastics using energy dispersion.

A key requirement for the development of the field of medical x-ray scatter imaging is accurate characterization of the differential scattering cross sections of tissues and phantom materials. The coherent x-ray scattering form factors of five tissues (fat, muscle, liver, kidney, and bone) obtained from butcher shops, four plastics (polyethylene, polystyrene, lexan (polycarbonate), nylon), and water have been measured using an energy-dispersive technique. The energy-dispersive technique has several improvements over traditional diffractometer measurements. Most notably, the form factor is measured on an absolute scale with no need for scaling factors. Form factors are reported in terms of the quantity x = λ(-1)sin (θ/2) over the range 0.363-9.25 nm(-1). The coherent form factors of muscle, liver, and kidney resemble those of water, while fat has a narrower peak at lower x, and bone is more structured. The linear attenuation coefficients of the ten materials have also been measured over the range 30-110 keV and parameterized using the dual-material approach with the basis functions being the linear attenuation coefficients of polymethylmethacrylate and aluminum.

An energy-dispersive technique to measure x-ray coherent scattering form factors of amorphous materials.

The material-dependent x-ray scattering properties of amorphous substances such as tissues and phantom materials used in imaging are determined by their scattering form factors, measured as a function of the momentum transfer argument, x. Incoherent scattering form factors, F(inc), are calculable for all values of x while coherent scattering form factors, F(coh), cannot be calculated except at large x because of their dependence on long-range order. As a result, measuring F(coh) is very important to the developing field of x-ray scatter imaging. Previous measurements of F(coh), based on crystallographic techniques, have shown significant variability, as these techniques are not optimal for amorphous materials. We have developed an energy-dispersive technique that uses a polychromatic x-ray beam and an energy-sensitive detector. We show that F(coh) can be measured directly, with no scaling parameters, by computing the ratio of two spectra: the first, measured at a given scattering angle and the second, the direct transmission spectrum with no scattering. Experiments have been constructed on this principle and used to measure F(coh) for water and polyethylene to explore the reliability of the technique. A 121 kVp x-ray spectrum and seven different scattering angles between 1.67 and 15.09 degrees were used, resulting in a measurable range of x between 0.5 and 9.5 nm(-1). These are the first measurements of F(coh) made without the need for a scaling factor. Resolution in x varies between 10% for small scattering angles and 2% for large scattering angles. Accuracy in F(coh) is shown to be strongly dependent on the precision of the experimental geometry and varies between 5% and 15%. Comparison with previous published measurements for water shows values of the average absolute relative difference between 8% and 14%.

Dural infiltration of metastatic Hodgkin's lymphoma.

Hodgkin's disease is a neoplasm of clonal Reed-Sternberg cells. Intracranial Hodgkin's lymphoma is rare. We present a unique case of a 57-year-old woman with secondary intracranial lymphoma infiltrating the dura. Her past medical history included Hodgkin's lymphoma from which she was deemed to be in remission at the time of presentation. Following an acute onset of seizures, she underwent radiological investigations that demonstrated an enhancing right-sided temporal dural-based space occupying lesion. Histopathological findings revealed nodular sclerosing Hodgkin's lymphoma with pathognomonic Reed-Sternberg cells. In cases of intracranial lesions with dural infiltration, Hodgkin's lymphoma should be considered in the diagnosis.

Contiguous synchronous occurrence of primary cerebral lymphoma and meningioma.

An unusual combination of primary cerebral lymphoma and meningioma occurring contiguously was encountered in a 71-year-old male patient. The possibility of two separate tumours was suspected radiologically and confirmed by histology. The association of primary lymphoma and meningioma is extremely rare. Following review of the literature, current evidence would suggest that the association is probably coincidental.

X chromosome influences sperm length in the stalk-eyed fly Cyrtodiopsis dalmanni.

Whether sexually selected traits are sex linked can have profound effects on their evolution. In the diopsid stalk-eyed fly, Cyrtodiopsis dalmanni, sperm length and female reproductive tract morphology have coevolved across species, postcopulatory sexual selection is known to occur, and X-linked genes affect female ventral sperm receptacle size. Here, we estimate the location of quantitative trait loci (QTL) for spermatocyst tail length by using F2 progeny segregating for an X-linked factor that causes sex-ratio meiotic drive. We found two QTL, including a major X-linked QTL responsible for 25% of the variation in spermatocyst tail length 2.1 cM from the sex-ratio element and 0.8 cM from a major eye span QTL. Sex-ratio males produce shorter spermatocyst tails and shorter eye spans. Thus, X-linked factors affect both pre- and postcopulatory traits, and linkage between the alleles for short eye span and short spermatocyst tail length allow pre- and postcopulatory sexual selection to potentially act in concert against the transmission bias caused by the sex-ratio chromosome.

Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni.

Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of XSR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that XSR/XST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.

Do female spiders select heavier males for the genes for behavioral aggressiveness they offer their offspring?

We explore the hypothesis that females choose to mate with heavier males for the genes for behavioral aggressiveness they offer their offspring in the desert spider, Agelenopsis aperta. Behavioral aggressiveness is important to competition for limited resources in the field and is thus correlated with the mass spiders achieve. We established four crosses based on the body mass relationships of parents subjected to selection in their natural environment (female mass/male mass: HI/HI, HI/LO, LO/HI, and LO/LO) and reared the F1 offspring in a noncompetitive laboratory environment. Offspring size and mass at maturity were measured, life history parameters recorded, and behavioral aggressiveness scored in a series of tests. Significant familial effects were detected in all of these measures, but pertinent cross effects were observed only in the assays measuring behavioral aggressiveness. The results were summarized in terms of the fitness costs to HI females of mating with LO males (fewer female offspring of the more aggressive phenotypes) and the benefits to LO females of mating with HI males (fewer fearful offspring of both sexes).

Interleukin-1beta exacerbates hypoxia-induced neuronal damage, but attenuates toxicity produced by simulated ischaemia and excitotoxicity in rat organotypic hippocampal slice cultures.

Using organotypic hippocampal slice cultures we have investigated the actions of Interleukin-1 (IL-1) in a number of injury paradigms. Low concentrations of IL-1 potentiated hypoxia-induced neurodegeneration whilst high concentrations had no effect. In contrast, higher concentrations of IL-1 were strongly neuroprotective in models of combined oxygen/glucose deprivation and N-methyl-D-aspartate toxicity, but no potentiation was observed at low IL-1 concentrations. Both protective and toxic effects of IL-1 were fully antagonized by IL-1 receptor antagonist. These data demonstrate that the effects of IL-1 on neuronal injury are complex, and may be directly related to the injury paradigm studied.

X-ray forward-scatter imaging: experimental validation of model.

In our research program we have investigated, through modeling and related numerical calculations, the potential use of scattered photons for medical x-ray imaging. In this work, we present an experimental validation of the primary and of the forward-scatter x-ray imaging models. Incident polyenergetic photon beams generated from a conventional rotating anode x-ray tube were used. To compare quantitatively the results between primary and forward-scatter imaging, an ionization chamber was used to record the incident air collision kerma, Kair(c). Plots of contrast (C) and the signal-to-noise ratio (SNR) as a function of the imaging task are presented. We have chosen to make measurements with plastics [polymethyl methacrylate (PMMA), polycarbonate, polystyrene, polyethylene, and nylon] placed at the center of a 15 cm diam spherical water phantom. Good agreement between experiment (expt) and prediction (pred) was obtained for many imaging tasks. For example, to image a 2 cm thick PMMA/polycarbonate combination using an 80 kV beam with the primary photons we obtain Cexpt = 0.01 +/- 0.02, Cpred = 0.008 +/- 0.002, SNRexp/square root Kair(c) = 0.86 +/- 1.6(mJ/kg)(-1/2) and SNRpred/square root K(air)c = 0.51 +/- 0.14(mJ/kg)(-1/2). The values obtained by using the theta = 4 degrees scattered field were Cexpt = 0.26 +/- 0.06, Cpred = 0.19 +/- 0.01, SNRexp/square root Kair(c) = 3.8 +/- 0.8(mJ/ kg)(-1/2), and SNRpred/square root K(air(c) = 3.2 +/- 0.3 (mJ/kg)(-1/2) We have, however, shown that using form factor data from different authors can have a significant effect on the predicted values of C and SNR. The use of our semianalytic expressions for the numbers of transmitted and scattered photons combined with our experimental measurements allowed us to quantify the amount of water contamination in our measurements. Some preliminary results in air with biological materials (liver, muscle, water) are also presented. We are confident that our model can be used as a tool for designing and optimizing an x-ray scatter imaging system.

Stability of a second-generation cephalosporin veterinary mastitis formulation after electron beam irradiation.

This study focused on the chemical stability of the cephalosporin (6R, 7R)-7-(1-pentafluorophenoxyacetamido)-3-[2-(5-methyl-1,3,4-thiodiazolyl)thiomethyl]-Delta(3)-cephem-4-carboxylic acid, sodium salt (cephem 1) formulation after electron beam (e-beam) irradiation. The cephem 1 concentrations of samples irradiated at 5, 10, and 15 kilograys for glass vials and low-density polyethylene (LDPE) cannula syringes were not statistically different from the concentrations of the nonirradiated control samples. Samples from each irradiation dose stored in controlled-temperature chambers at 5 degrees C and 30 degrees C for 24 months did not show any concentration changes within statistical limits compared with the nontreated samples. Samples from each irradiation dose stored at 40 degrees C for 12 months also did not show any concentration changes within statistical limits compared with the nontreated samples. The percentage of related substances increased slightly with the increase in e-beam irradiation level and storage temperature, but this increase was within the proposed label claim of 90% to 110% (45-55 mg/g). In conclusion, e-beam sterilization did not affect the chemical stability of cephem 1 intramammary formulation in LDPE cannula syringes, suggesting that e-beam irradiation may be a feasible method for terminal sterilization of this cephem 1 formulation.

High-level expression of biologically active human prolactin from recombinant baculovirus in insect cells.

We examined the feasibility of high-level production of recombinant human prolactin, a multifunctional protein hormone, in insect cells using a baculovirus expression system. The human prolactin cDNA with and without the secretory signal sequence was cloned into pFastBac1 baculovirus vector under the control of polyhedrin promoter. Prolactin was produced upon infection of either Sf9 or High-Five cells with the recombinant baculovirus containing the human prolactin cDNA. The production of recombinant prolactin varied from 20 to 40 mg/L of monolayer culture, depending on the cell types. The prolactin polypeptide with its own secretory signal was secreted into the medium. N-terminal amino acid sequence analysis of the recombinant polypeptide purified from the culture medium indicated that the protein was processed similar to human pituitary prolactin. Carbohydrate analysis of the purified protein indicated that a fraction of the recombinant prolactin made in insect cells appeared to be glycosylated. Also, both secreted and nonsecreted forms of the recombinant prolactin in insect cells were biologically equivalent to the native human prolactin (pituitary derived) in the Nb2 lymphoma cell proliferation assay.

Glucose-based oligosaccharides exhibit different in vitro fermentation patterns and affect in vivo apparent nutrient digestibility and microbial populations in dogs.

To evaluate the potential of indigestible oligosaccharides (OS) to serve as "dietary fiber-like" ingredients, it is necessary to determine their extent of indigestibility. In vitro fermentation characteristics of two novel OS, alpha-glucooligosaccharides (GOS) and a maltodextrin-like OS (MD), were compared to those of fructooligosaccharides (FOS), gum arabic (GA), guar gum (GG) and guar hydrolysate (GH). Total short-chain fatty acid (SCFA) production (micromol/g dry matter) as a result of MD fermentation was higher initially compared with GA (P<0.01), but GA was more extensively fermented at 24 h (P<0.01). Total SCFA production for GOS was similar to that for FOS, GG, GH and GA. In the second experiment, GOS and MD were added at 6% to an enteral formula control diet (Control) and fed to ileal-cannulated dogs in a 3x3 replicated Latin-square design. Ileal digestibility of glucose was lower (P<0.05) and carbohydrate (CHO) numerically lower (P = 0.08) for both GOS and MD compared with the Control. Total tract digestibility of CHO and glucose was lower only for MD (P<0.01) compared with the Control. Total fecal weights were higher (P<0.01) for both GOS and MD treatments. Fecal concentration of bifidobacteria was numerically increased by GOS and MD supplementation (P = 0.13 and 0.23, respectively). Thus, GOS and MD are indigestible yet fermentable OS, and may act as "dietary fiber-like" ingredients.

Analysis of spectral blur effects in x-ray scatter imaging.

Previous analysis in our research program investigating the potential use of scattered photons for medical x-ray imaging has been for monoenergetic beams. In practice, polyenergetic beams are almost always used due to their higher photon fluence rate. The effects of beam polychromaticity on x-ray scatter imaging are determined with the aid of our semianalytic model that images a target object against a background material of the same dimensions when both are situated within a water phantom. Our analysis involves four different photon beams with constant incident energy fluence: (1) a monoenergetic beam with photon energy E0, (2) a dual peak beam with two separate monoenergetic peaks of energies E1 and E2, (3) a clinical x-ray beam, and (4) a rectangular beam with uniform energy fluence between energies Emin and Emax. A comparison between the polyenergetic spectra is accomplished by matching the centroids and standard deviations of the dual peak and rectangular spectra to those of the clinical x-ray spectrum. For the task of imaging liver versus fat structures 1 cm thick in a 25-cm-diam spherical water phantom with the scattered photons between 2 degrees and 12 degrees, the predicted signal-to-noise ratio (SNR) obtained with a 100 kV beam is 87.5% of the SNR acquired with the optimum monoenergetic beam (SNRopt). The SNR for the corresponding dual peak beam is 84.4% of SNRopt and for the rectangular beam is 86.3%. Our analysis shows that monoenergetic x-ray beams are not necessary for x-ray scatter imaging.

Photon-counting radiography with the gas microstrip detector.

We have built a proof of-concept photon-counting x-ray imaging system using a Xe:CH4 gas microstrip detector (GMD) as the image receptor, and have used this system to demonstrate several advantages of photon counting over energy integration. Our experiments spanned x-ray spectra from 10 to 50 kVp and Xe:CH4 pressures from 1 to 4 atm. When photon counting is done, the energy deposited in the detector by each incident photon can be measured on adjacent anode strips and a centroid calculation can be used to provide spatial resolution significantly better than the anode strip pitch. We measured > 11 lp mm(-1) at 13 kVp with our 200 microm pitch detector, and 8.2 lp mm(-1) at 50 kVp. The energy resolution of our GMD is 5.2% at 59.6 keV, and the space-charge limited counting rate is >2 x 10(6) mm(-2) s(-1) at 3 atm for a 30 kVp beam.

Improving patient outcomes through CQI: vascular access planning.

This article reports the use of the continuous quality improvement (CQI) process to improve patient outcomes. The FADE method (focus, analyze, develop, and execute) was used to focus on vascular access planning, analyze data concerning intravenous (i.v.) therapy, develop a vascular access planning algorithm, and execute implementation of the algorithm. An evaluation study revealed that patients whose vascular access planning was consistent with the algorithm reported fewer i.v.s, less difficulty starting i.v.s, and less stress; waited significantly less time until central venous line (CVL) placement (for those who received CVLs); and had significantly shorter lengths of stay.

Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome.

STUDY OBJECTIVE: To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes. METHODS: We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale. RESULTS: We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63). CONCLUSION: One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.

A semianalytic model to investigate the potential applications of x-ray scatter imaging.

Although x-ray scatter is generally regarded as a nuisance that reduces radiographic contrast (C) and the signal-to-noise ratio (SNR) in conventional images, many technologies have been devised to extract useful information from the scattered x rays. A systematic approach, however, for analyzing the potential applications of x-ray scatter imaging has been lacking. Therefore, we have formulated a simple but useful semianalytic model to investigate C and SNR in scatter images. Our model considers the imaging of a target object against a background material of the same dimensions when both are situated within a water phantom. We have selected biological materials (liver, fat, bone, muscle, blood, and brain matter) for which intermolecular form factors for coherent scattering were available. Analytic relationships between C and SNR were derived, and evaluated numerically as the target object thickness (0.01-40 mm) and photon energy (10-200 keV) were systematically varied. The fundamental limits of scatter imaging were assessed via calculations that assumed that all first-order scatter exiting the phantom, over 4 pi steradians, formed the signal. Calculations for a restricted detector solid angle were then performed. For the task of imaging white brain matter versus blood in a 15 cm thick water phantom, the maximum SNR, over all energies, for images based on the detection of all forward scatter within the angular range 2 degrees-12 degrees is greater than that of primary images for target object thicknesses < or = 23 mm. Use of the backscattered x rays within the range 158 degrees-178 degrees to image objects 3 cm below the surface of a 25 cm thick water phantom allows the liver to be distinguished from fat with a SNR superior to that of primary imaging when the objects are < or = 22 mm thick. Our analysis confirms the usefulness of scattered x rays, and provides simple methods for determining the regimes of medical interest in which x-ray scatter imaging could outperform conventional imaging.