Net present value analysis to select public r&d programs and valuate expected private sector participation

Applied Biochemistry and Biotechnology - One of the main functions of government is to invest taxpayer dollars in projects, programs, and properties that will result in social benefit. Public...     

Validity and Reliability of the Reflux Symptom Index (RSI)

Laryngopharyngeal reflux (LPR) is present in up to 50% of patients with voice disorders. Currently, there is no validated instrument that documents symptom severity in LPR. We developed the reflux symptom index (RSI), a self-administered nine-item outcomes instrument for LPR. The purpose of this investigation was to evaluate the psychometric properties of the RSI. For validity assessment, 25 patients with LPR were evaluated prospectively before and six months after b.i.d. treatment with proton pump inhibitors (PPI). Each patient completed the RSI as well as the 30-item voice handicap index (VHI). For reliability assessment, the study patients were given the RSI on two separate occasions before the initiation of treatment. Normative RSI data were derived from 25 age-matched and gender-matched controls taken from an existing database of asymptomatic individuals without any evidence of LPR. The mean RSI (+/- standard deviation) of patients with LPR improved from 21.2 (+/- 10.7) to 12.8 (+/- 10.0), and the mean VHI improved from 52.2 (+/- 24.7) to 41.5 (+/- 25.0) after 6 months of therapy (p = 0.001 and 0.065, respectively). Of the three VHI subscales (emotional, physical, functional), only the functional subscale improved significantly (p = 0.037). Patients who experienced a five point or better improvement in RSI were 11 times more likely to experience a five-point improvement in VHI (95% confidence interval = 1.7, 76.8). For reliability assessment, the first and second pretreatment RSIs were 19.9 (+/- 11.1) and 20.9 (+/- 9.6), respectively (correlation coefficient = 0.81, p < 0.001). The single-item correlation coefficients ranged from 0.41 to 0.91 (p < 0.05 for all items). The mean pretreatment RSI in patients with LPR was significantly higher than controls (21.2 versus 11.6; p < 0.001). The mean RSI of patients with LPR after 6 months of PPI therapy approached that of asymptomatic controls (p > 0.05). The RSI is easily administered, highly reproducible, and exhibits excellent construct and criterion-based validity.     

Fibronectin: An Interesting Vocal Fold Protein

A great deal of information is accruing regarding the function of the extracellular matrix. Once thought to be simply a structural entity to surround cells, it is now known to do much more. Fibronectin in particular has received specific attention. Fibronectin is a ubiquitous glycoprotein found most abundantly in the extracellular matrix of regenerating, healing, and embryonic tissue. Vast evidence supports the fact that fibronectin participates in many diverse functions throughout the body that are relevant to vocal fold biology. This article introduces the structure of fibronectin and its isoforms and provides an introduction to some of the many functions it plays. It also reviews the evidence about fibronectin's place in vocal folds and vocal fold pathology. It discusses fibronectin's presence in vocal nodules, vocal polyps, vocal scarring, and Reinke's edema, and reviews the data on its role in mucosal wave impairment. Lastly, it discusses preliminary microarray data that show gene expression for fibronectin to be upregulated in true vocal folds when compared to false vocal folds.     

Short-Term Therapeutic Trial of Proton Pump Inhibitors in Suspected Extraesophageal Reflux

Pharyngoesophageal gastric acid reflux is thought to initiate chronic posterior laryngitis. The gold standard for measuring gastric reflux is dual-channel 24-hour pH monitoring. This is a time-consuming, inconvenient, expensive method that is not available in all areas. New therapeutic regimes that make use of proton pump inhibitors (PPIs) have proven to be therapeutically efficient for control of acid reflux. Twenty-four consecutive patients with chronic voice disorders and signs of posterior laryngitis were selected for therapy. Twenty-four hour pH monitoring was performed independently before the therapy. The trial therapy consisted of all patients receiving pantoprazole, 40 mg once daily for 6 weeks. Immediately following the therapy a statistically significant (p < 0.05) improvement was observed in all patients. This improvement was analyzed retrospectively by comparison with the results of 24-hour pH monitoring. In 71% of the patients the 24-hour pH-monitoring gave a positive result showing a high number of patients with extraesophageal reflux in our study group. Patients with positive results of pH-monitoring responded in a statistically significant manner (p < 0.05) to the pantoprazole therapy, whereas those patients without detected reflux did not. A 3-month follow-up of the patients with a positive result of the pH-monitoring confirmed the improvement. No patients reported adverse effects. A 6-week treatment with pantoprazole can be clinically justified. It helps to save time and reduce costs, allows for selection of reflux-negative patients for alternative therapy, and may prevent inadequate treatment of patients with false-negative pH monitoring. Twenty-four hour pH monitoring is still recommended for patients unresponsive to this trial therapy.     

Electrophysiologic monitoring of the recurrent laryngeal nerves may not predict bilateral vocal fold immobility after thyroid surgery

Two cases of bilateral vocal fold immobility (VFI) after identification and preservation of the recurrent laryngeal nerves (RLNs) required tracheotomy until vocal fold recovery. The first patient underwent thyroid surgery without preoperative or postoperative evaluation of the vocal folds, administration of postoperative intravenous steroids, or electrophysiologic monitoring of the RLNs, whereas the second patient underwent a thyroid procedure in which all of the aforementioned were executed. Preoperative and postoperative clinical evaluation of the RLNs is strongly suggested in patients undergoing thyroid surgery, especially revision surgery. Patients potentially undergoing total thyroidectomy should be counseled about the remote chance of airway obstruction and should be properly selected for this operation. Subclinical stretching of the RLNs or ischemia from the endotracheal tube cuff can result in unilateral VFI, and rarely bilateral VFI, requiring reintubation, tracheotomy, or vocal fold lateralization. Electrophysiologic monitoring may not always predict bilateral VFI.     

Topologically weakly mixing homeomorphisms of the Klein bottle that are uniformly rigid

In this paper we prove that there is a large family of topologically weakly mixing homeomorphisms of the Klein bottle that are uniformly rigid. We do this by viewing the Klein bottle as the quotient of the two-torus by an appropriate group action and producing topologically weakly mixing homeomorphisms of the two-torus that are uniformly rigid and equivariant with respect to the action.     

Stability and convergence of the spectral Lagrange-Galerkin method for mixed periodic/non-periodic convection-dominated diffusion problems

We present a convergence analysis of the spectral Lagrange-Galerkinmethod for mixed periodic/non-periodic convection-diffusionproblems. The scheme is unconditionally stable, independentof the diffusion coefficient, even in the case when numericalquadrature is used. The theoretical predictions are illustratedby a series of numerical experiments. For the periodic case,our results present a significant improvement on those givenby Süli & Ware (1991) SIAM J. Numer.Anal.28, 423-445).     

Uptake and trafficking of mildly oxidized LDL and acetylated LDL in THP-1 cells does not explain the differences in lysosomal metabolism of these two lipoproteins.

Foam cells in the atherosclerotic lesion have substantial cholesterol stores within large, swollen lysosomes. This feature is mimicked by incubating THP-1 macrophages with mildly oxidized low density lipoprotein (LDL). Incubation of THP-1 cells with acetylated LDL produces cytoplasmic cholesteryl ester accumulation rather than lysosomal storage. The differences could be due to differences in uptake and delivery of lipoprotein to lysosomes or to lysosomal and post-lysosomal processing events. We compared uptake and lysosomal trafficking of acetylated and oxidized LDL using colloidal gold-labeled lipoproteins. Labeling did not alter cellular cholesterol accumulation. We found that uptake and delivery to lysosomes are not different for acetylated and oxidized LDL. In fact, both oxidized and acetylated LDL can be delivered to the same lysosomes. Sequential incubation with oxidized LDL followed by acetylated LDL showed that the lipid-engorged lysosomes are long-lived structures, continuously accepting newly ingested lipoprotein. Comparison of acetylated and oxidized LDL in mouse peritoneal macrophages, a cell which does not accumulate substantial lysosomal lipid, also revealed no differences in uptake. This indicates that in THP-1 cells, the differences in metabolism of oxidized and acetylated LDL are due to cell-specific lysosomal or post-lysosomal events not present in B6C3F1 mouse macrophages.     

Sorption of arsenic, cadmium, and lead by chars produced from fast pyrolysis of wood and bark during bio-oil production

Bio-char by-products from fast wood/bark pyrolyses, were investigated as adsorbents for the removal of the toxic metals (As(3+), Cd(2+), Pb(2+)) from water. Oak bark, pine bark, oak wood, and pine wood chars were obtained from fast pyrolysis at 400 and 450 degrees C in an auger-fed reactor and characterized. A commercial activated carbon was also investigated for comparison. Chars were sieved (>600, 600-250, 250-177, 177-149, and <149 microm) and the particle size fraction from 600 to 250 microm was used without further modification for all studies unless otherwise stated. Sorption studies were performed at different temperatures, pHs, and solid to liquid ratios in the batch mode. Maximum adsorption occurred over a pH range 3-4 for arsenic and 4-5 for lead and cadmium. Kinetic studies yielded an optimum equilibrium time of 24 h with an adsorbent dose of 10 g/L and concentration approximately 100 mg/L for lead and cadmium. Sorption isotherms studies were conducted in broad concentration ranges (1-1000 ppb for arsenic, 1x10(-5)-5x10(-3) M for lead and cadmium). Oak bark out-performed the other chars and nearly mimicked Calgon F-400 adsorption for lead and cadmium. In an aqueous lead solution with initial concentration of 4.8x10(-4) M, both oak bark and Calgon F-400 (10 g/L) removed nearly 100% of the heavy metal. Oak bark (10 g/L) also removed about 70% of arsenic and 50% of cadmium from aqueous solutions. Varying temperatures (e.g., 5, 25, and 40 degrees C) were used to determine the effect of temperatures. The equilibrium data were modeled with the help of Langmuir and Freundlich equations. Overall, the data are well fitted with both the models, with a slight advantage for Langmuir model. The oak bark char's ability to remove Pb(II) and Cd(II) is remarkable when considered in terms of the amount of metal adsorbed per unit surface area (0.5157 mg/m(2) for Pb(II) and 0.213 mg/m(2) for Cd(II) versus that of commercial activated carbon.