Intravaginal Controlled Administration of Flurogestone Acetate: (III) Development of Rate-Control Vaginal Devices

A Rate-Control vaginal device was developed which overcomes the low bioavailability and unpredictable Q - t^1/2 type release and absorption rate profiles of flurogestone acetate delivered by the currently marketed Syncro-Mate pessary.

The in vitro release and vaginal absorption profiles from the Rate-Control vaginal device were run simultaneously, a linear Q - t relationship was obtained with a significant improvement in bioavailability. A mathematical model was developed to correlate the in vitro drug release and the vaginal absorption profiles of flurogestone acetate from the vaginal devices.

The design, development and the simultaneous release and absorption profiles of flurogestone acetate from this new vaginal device were outlined and discussed.     

RADIAL FLOW HOLLOW FIBERREVERSE OSMOSIS: EXPERIMENTS AND THEORY

The performance of a hollow fiber reverse osmosis system is studied both theoretically and experimentally. Experiments were carried out for applied pressure ranging from 200 to 400 psig, feed rates varying from 75 to 380 cc/sec and for feed concentrations up to 34,000 ppm of sodium chloride.

A mathematical model is proposed to predict productivity, ϕ, and product concentration, θ_p. The model involves solving membrane transport equations simultaneously with the hydrodynamic equations. The solubility-diffusion-imperfection, or pore diffusion model, is used to describe solute and solvent transport across the membrane. The axial gradients of shell side concentration, neglected in previous investigations, are taken into account. The differential equations are solved numerically by the 4th Order Runge-Kutta method.

Predicted values of ϕ and θ_p agree within 8% and 17% respectively, with experimental data over the entire range of operating conditions. However, membrane transport coefficients were found to be concentration dependent.

An approximate analysis shows that the concentration polarization is negligible in present day hollow fiber systems.     

Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation

Traumatic brain injury (TBI) induces secondary biochemical changes that contribute to delayed neuroinflammation, neuronal cell death, and neurological dysfunction. Attenuating such secondary injury has provided the conceptual basis for neuroprotective treatments. Despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed. In part, these failures likely reflect methodological differences between the clinical and animal studies, as well as inadequate pre-clinical evaluation and/or trial design problems. However, recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation. Here we critically analyze the current limitations and translational opportunities for developing successful neuroprotective therapies for TBI.     

A single-period perishable inventory model where deterioration begins at a random point in time

This paper develops a single-period inventory model where the stock begins to deteriorate at a random point in time within the period. Once this deterioration begins, the selling price can be adjusted once at that point. Optimum order size and pricing policies are determined for such an inventory model through a numerical illustration.     

Characterization of the physicochemical and structural evolution of biomass particles during combined pyrolysis and CO2 gasification

The combination of pyrolysis and CO₂ gasification was studied to synergistically improve the syngas yield and biochar quality. The subsequent 60-min CO₂ gasification at 800 °C after pyrolysis increased the syngas yield from 23.4% to 40.7% while decreasing the yields of biochar and bio-oil from 27.3% to 17.1% and from 49.3% to 42.2%, respectively. The BET area of the biochar obtained by the subsequent 60-min CO₂ gasification at 800 °C was 384.5 m²/g, compared to 6.8 m²/g for the biochar obtained by the 60-min pyrolysis at 800 °C, and 1.4 m²/g for the raw biomass. The biochar obtained above 500 °C was virtually amorphous.     

Influence of age on optimal daily levothyroxine dosage in patients with primary hypothyroidism grouped according to etiology

BACKGROUND: Optimal daily levothyroxine (LT4) dosage is reported to be significantly smaller in the elderly with primary hypothyroidism when compared with their younger counterparts. However, this finding has not been studied in different etiologic groups. METHODS: This study assessed the influence of age on optimal daily LT. dosage in 337 patients with primary hypothyroidism grouped according to etiology. RESULTS: Daily LT. dosage declined with increasing age in 99 patients with Hashimoto's thyroiditis, in 73 patients with idiopathic variety, and in 47 patients with hypothyroidism due to radical neck surgery and/or neck radiation for non-thyroidal malignancies. In contrast, daily LT. dosage rose with age in 85 patients who had radioiodine (131I) therapy and/or subtotal thyroidectomy for hyperthyroidism. Finally, daily LT. dosage was not significantly altered in 22 patients with subclinical hypothyroidism or in 11 patients with drug-induced hypothyroidism. CONCLUSION: Optimal daily LT4 dosage does not decline universally in all elderly with primary hypothyroidism: it appears to depend also on the etiology of the disorder.     

TSP Heuristics: Domination Analysis and Complexity

   Abstract. We show that the 2-Opt and 3-Opt heuristics for the traveling salesman problem (TSP) on the complete graph K _n produce a solution no worse than the average cost of a tour in K _n in a polynomial number of iterations. As a consequence, we get that the domination numbers of the 2- Opt , 3- Opt , Carlier—Villon, Shortest Path Ejection Chain, and Lin—Kernighan heuristics are all at least (n-2)! / 2 . The domination number of the Christofides heuristic is shown to be no more than

TSP Heuristics: Domination Analysis and Complexity

We show that the 2-Opt and 3-Opt heuristics for the traveling salesman problem (TSP) on the complete graph Kn produce a solution no worse than the average cost of a tour in Kn in a polynomial number of iterations. As a consequence, we get that the domination numbers of the 2- Opt , 3- Opt , Carlier—Villon, Shortest Path Ejection Chain, and Lin—Kernighan heuristics are all at least (n-2)! / 2 . The domination number of the Christofides heuristic is shown to be no more than $\lceil{n}/{2}\rceil !$ , and for the Double Tree heuristic and a variation of the Christofides heuristic the domination numbers are shown to be one (even if the edge costs satisfy the triangle inequality). Further, unless P = NP, no polynomial time approximation algorithm exists for the TSP on the complete digraph $\vec{K}_n$ with domination number at least (n-1)!-k for any constant k or with domination number at least (n-1)! - (( k /(k+1))(n+r))!-1 for any non-negative constants r and k such that (n+r) $\equiv$ 0 mod (k+1). The complexities of finding the median value of costs of all the tours in $\vec{K}_n$ and of similar problems are also studied.     

Clustering problems in optimization models

We discuss a variety of clustering problems arising in combinatorial applications and in classifying objects into homogenous groups. For each problem we discuss solution strategies that work well in practice. We also discuss the importance of careful modelling in clustering problems.Part of this work was carried out while the author was visiting the IOE Department, University of Michigan on a CNR fellowship. Author for correspondence     

Intravaginal Controlled Administration of Flurogestone Acetate: (IV) In Vitro - In Vivo Correlation for Intravaginal Drug Delivery from Rate-Control Vaginal Pessary

One hundred fifty sheep received various types of Rate-Control vaginal pessaries for a period of up to 19 days at various geographic locations. As predicted from the in vitro studies, a constant (Q - t) absorption profile was also observed in in vivo. The effect of the loading dose of flurogestone acetate on the in vitro and in vivo absorption profiles were examined and minimum effective loading dose was determined. An excellent the prediction of the long-term (19-day) in vivo absorption profiles from a short-term (3-day) in vitro absorption study.