Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Background: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs) and ratio of individual predicted to observed concentration (Cipred/Cobs) as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history. Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the "Depression: The search for treatment relevant phenotypes" study), was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram). Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history. Results: Simulations for those scenarios representing a known dosing history were generated from historical MEMS data. Simulations of a long half-life drug exhibited a trend for overprediction of concentrations in patients with a low percentage of doses taken and underprediction of concentrations in patients taking more than their prescribed number of doses. Overall, the ratios did not predict adherence well, except when the true adherence rates were extremely high (greater than 100% of prescribed doses) or extremely low (complete nonadherence). In general, the Cipred/Cobs ratio was a better predictor of adherence rate than the Cpred/Cobs ratio. Correct predictions of extreme (high, low) 7-day adherence rates using Cipred/Cobs were 73.8% and 64.0%. Conclusion: This simulation study demonstrated the limitations of the Cpred/obs and Cipred/obs ratios as metrics for actual dosage intake history, and identified that use of MEMS dosing history monitoring combined with sparse pharmacokinetic sampling is a more reliable approach. © 2011 Feng et al

Ear-clipping Based Algorithms of Generating High-quality Polygon Triangulation

A basic and an improved ear clipping based algorithm for triangulating simple polygons and polygons with holes are presented. In the basic version, the ear with smallest interior angle is always selected to be cut in order to create fewer sliver triangles. To reduce sliver triangles in further, a bound of angle is set to determine whether a newly formed triangle has sharp angles, and edge swapping is accepted when the triangle is sharp. To apply the two algorithms on polygons with holes, "Bridge" edges are created to transform a polygon with holes to a degenerate polygon which can be triangulated by the two algorithms. Applications show that the basic algorithm can avoid creating sliver triangles and obtain better triangulations than the traditional ear clipping algorithm, and the improved algorithm can in further reduce sliver triangles effectively. Both of the algorithms run in O(n2) time and O(n) space.Comment: Proceedings of the 2012 International Conference on Information Technology and Software Engineering Lecture Notes in Electrical Engineering Volume 212, 2013, pp 979-98

Gonadotropic activity of a second relaxin-type peptide in starfish.

In starfish, a relaxin-like gonad-stimulating peptide (RGP) acts as a gonadotropin that triggers gamete maturation and spawning. In common with other relaxin/insulin superfamily peptides, RGP consists of an A- and a B-chain, with cross-linkages mediated by one intra- and two inter-chain disulfide bonds. In this study, a second relaxin-like peptide (RLP2) was identified in starfish species belonging to the orders Valvatida, Paxillosida, and Forcipulatida. Like RGP, RLP2 precursors comprise a signal peptide and a C-peptide in addition to the A- and B-chains. However, a unique cysteine motif [CC-(3X)-C-(10X)-C] is present in the A-chain of RLP2, which contrasts with the cysteine motif in other members of the relaxin/insulin superfamily [CC-(3X)-C-(8X)-C]. Importantly, in vitro pharmacological tests revealed that Patiria pectinifera RLP2 (Ppe-RLP2) and Asterias rubens RLP2 (Aru-RLP2) trigger shedding of mature eggs from ovaries of P. pectinifera and A. rubens, respectively. Furthermore, the potencies of Ppe-RLP2 and Aru-RLP2 as gonadotropic peptides were similar to those of Ppe-RGP and Aru-RGP, respectively, and the effect of RLP2 exhibited partial species-specificity. These findings indicate that two relaxin-type peptides regulate spawning in starfish and therefore we propose that RGP and RLP2 are renamed RGP1 and RGP2, respectively

Counting Orbifolds

We present several methods of counting the orbifolds C^D/Gamma. A correspondence between counting orbifold actions on C^D, brane tilings, and toric diagrams in D-1 dimensions is drawn. Barycentric coordinates and scaling mechanisms are introduced to characterize lattice simplices as toric diagrams. We count orbifolds of C^3, C^4, C^5, C^6 and C^7. Some remarks are made on closed form formulas for the partition function that counts distinct orbifold actions.Comment: 69 pages, 9 figures, 24 tables; minor correction

Online Marking System for Vula

The University of Cape Town is in the process to migrate its course contents from a disparate number of learning management systems to the new Vula system. As the management of course contents is often done using different systems through various interfaces, Vula will be providing a common solution to all elearning needs at UCT. However, Vula does not currently provide a tool that allows the creation of marking guides and the subsequent use of such a marking guide for inputting marks and comments as feedbacks to students. This report describes the process of creating such a tool - the Vula Marking System , as it aims to solve the above problem, using J2EE and JavaScript Technologies, and essentially acts as a single entry point for all input of marks into Vula

Symmetries of Abelian Orbifolds

Using the Polya Enumeration Theorem, we count with particular attention to C^3/Gamma up to C^6/Gamma, abelian orbifolds in various dimensions which are invariant under cycles of the permutation group S_D. This produces a collection of multiplicative sequences, one for each cycle in the Cycle Index of the permutation group. A multiplicative sequence is controlled by its values on prime numbers and their pure powers. Therefore, we pay particular attention to orbifolds of the form C^D/Gamma where the order of Gamma is p^alpha. We propose a generalization of these sequences for any D and any p.Comment: 75 pages, 13 figures, 30 table

Remarks on quiver gauge theories from open topological string theory

We study effective quiver gauge theories arising from a stack of D3-branes on certain Calabi-Yau singularities. Our point of view is a first principle approach via open topological string theory. This means that we construct the natural A-infinity-structure of open string amplitudes in the associated D-brane category. Then we show that it precisely reproduces the results of the method of brane tilings, without having to resort to any effective field theory computations. In particular, we prove a general and simple formula for effective superpotentials

Curettage after uterine artery embolization combined with methotrexate treatment for caesarean scar pregnancy.

In the present study, we evaluated the diagnosis and management modalities of caesarean scar pregnancy (CSP). Thirty patients diagnosed with CSP were retrospectively studied between February, 2010 and February, 2012. Twenty-five patients were offered prophylactic uterine artery embolization (UAE) and methotrexate (MTX) prior to uterine suction curettage. Five cases were referred from other hospitals where the initial management with uterine suction curettage had resulted in uncontrollable massive haemorrhage, 4 of the cases had UAE and one proceeded immediately to hysterectomy. In the 25 patients treated with prophylactic UAE and MTX, 12 had laparoscopy-guided curettage and 13 had ultrasound-guided curettage without complication. The results showed that the 25 patients with CSP, who received prophylactic UAE and MTX prior to uterine curettage, recovered without complications. Five patients referred from other hospitals, where uterine curettage was the primary procedure, had severe complications including uncontrolled vaginal bleeding and uterine rupture. Four of the five patients were treated successfully with emergency UAE and the remaining patient underwent emergency hysterectomy as ultrasound examination detected significant haemorrhage between the uterus and the bladder. Of the 25 patients who received prophylactic UAE combined with MTX, there were no reports of irregular menstruation or serious adverse effects. Notably, the decrease in serum human chorionic gonadotropin (HCG) levels 3 days post-surgery was greater with ultrasound-guided curettage (84.3±5.5%) than with laparoscopy-guided curettage (76.3±10.2%). In summary, the data suggested that prophylactic UAE with MTX followed by ultrasound-guided curettage is the most effective therapeutic approach in CSP

D-branes Wrapped on Fuzzy del Pezzo Surfaces

We construct classical solutions in quiver gauge theories on D0-branes probing toric del Pezzo singularities in Calabi-Yau manifolds. Our solutions represent D4-branes wrapped around fuzzy del Pezzo surfaces. We study the fluctuation spectrum around the fuzzy CP^2 solution in detail. We also comment on possible applications of our fuzzy del Pezzo surfaces to the fuzzy version of F-theory, dubbed F(uzz) theory.Comment: 1+42 pages, 9 figures v2: references added v3: statements on the structure of the Yukawa couplings weakened. published versio

The Maximal U(1)LU(1)_L Inverse Seesaw from d=5d=5 Operator and Oscillating Asymmetric Sneutrino Dark Matter

The maximal $U(1)_L$ supersymmetric inverse seesaw mechanism (M$L$SIS) provides a natural way to relate asymmetric dark matter (ADM) with neutrino physics. In this paper we point out that, M$L$SIS is a natural outcome if one dynamically realizes the inverse seesaw mechanism in the next-to minimal supersymmetric standard model (NMSSM) via the dimension-five operator $(N)^2S^2/M_*$, with $S$ the NMSSM singlet developing TeV scale VEV; it slightly violates lepton number due to the suppression by the fundamental scale $M_*$, thus preserving $U(1)_L$ maximally. The resulting sneutrino is a distinguishable ADM candidate, oscillating and favored to have weak scale mass. A fairly large annihilating cross section of such a heavy ADM is available due to the presence of singlet.Comment: journal versio