A two-dimensional mathematical model of percutaneous drug absorption

Background When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface. Methods Though a simple one-dimensional model is often useful to describe percutaneous drug absorption, it may be better represented by multi-dimensional models. A two-dimensional mathematical model is developed for percutaneous absorption of a drug, which may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. This model consists of a linear second-order parabolic equation with appropriate initial conditions and boundary conditions. These boundary conditions are of Dirichlet type, Neumann type or Robin type. A finite-difference method which maintains second-order accuracy in space along the boundary, is developed to solve the parabolic equation. Extrapolation in time is applied to improve the accuracy in time. Solution of the parabolic equation gives the concentration of the drug in the skin at a given time. Results Simulation of the numerical methods described is carried out with various values of the parameter r. The illustrations are given in the form of figures. Conclusion Based on the values of r, conclusions are drawn about (1) the flow rate of the drug, (2) the flux and the cumulative amount of drug eliminated into the receptor cell, (3) the steady-state value of the flux, (4) the time to reach the steady-state value of the flux and (5) the optimal value of r, which gives the maximum absorption of the drug. The paper gives valuable information which can be obtained by this two-dimensional model, that cannot be obtained with one-dimensional models. Thus this model improves upon the much simpler one-dimensional models. Some future directions of the work based on this model and the one-dimensional non-linear models that exist in the literature, are also discussed

Online Privacy, Vulnerabilities, and Threats: A Manager’s Perspective

There are many potential threats that come with conducting business in an online environment. Management must find a way to neutralize or at least reduce these threats if the organization is going to maintain viability. This chapter is designed to give managers an understanding, as well as the vocabulary needed to have a working knowledge of online privacy, vulnerabilities, and threats. The chapter also highlights techniques that are commonly used to impede attacks and protect the privacy of the organization, its customers, and employees. With the advancements in computing technology, any and all conceivable steps should be taken to protect an organization’s data from outside and inside threats

Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

Kenneth T Cheng1, Hannah Y Cheng2, Kam Leung31Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Freelance Technical Writer, New Orleans, LA, USA; 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USAAbstract: Contrast-enhanced magnetic resonance imaging (CE-MRI) is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs) or pharmaceuticals approved for clinical imaging of the central nervous system (CNS) in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs) which do not penetrate the CNS blood–brain barrier (BBB). These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BT-DO3A, Gadovist™) is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r1 relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA) in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T1 shortening per unit volume than other clinical GBCAs which are only available in 0.5 M concentration. This double concentration of Gd-BT-DO3A may allow a relatively higher concentration of the agent to localize in the CNS and produce a better contrast enhancement at the same clinical dose as other GBCAs. Several recent published multicenter clinical trials appeared to support this potential advantage of Gd-BT-DO3A.Keywords: Gadovist, Gd-BT-DO3A, CE-MRI, CNS imaging, MRI contrast agent, gadoliniu

Hong Kong Style Urban Conservation

An invited conference paperConference Title: Heritage - driver of developmentTheme 1: Heritage and regional development, Session 1:Heritage but which one?This paper examines the evolution of the field of conservation in the city of Hong Kong. In particular, highlighting the ways in which conservation and urban development can be complementary forces instead of in opposition. The city of Hong Kong will be briefly introduced, along with the characteristics that define and influence its conservation, before moving on to the catalyst for Hong Kong’s conservation paradigm shift. The paper will proceed to highlight the various conservation initiatives embarked upon by the Hong Kong SAR’s Development Bureau, concluding with a discussion of the bureau’s accomplishments and challenges for the future.postprintThe 17th ICOMOS General Assembly and Scientific Symposium, Paris, France, 27 November-2 December 2011

Subwavelength localization and toroidal dipole moment of spoof surface plasmon polaritons

We experimentally and theoretically demonstrate subwavelength scale localization of spoof surface plasmon polaritons at a point defect in a two-dimensional groove metal array. An analytical expression for dispersion relation of spoof surface plasmon polaritons substantiates the existence of a band gap where a defect mode can be introduced. A waveguide coupling method allows us to excite localized spoof surface plasmon polariton modes and measure their resonance frequencies. Numerical calculations confirm that localized modes can have a very small modal volume and a high Q factor both of which are essential in enhancing light-matter interactions. Interestingly, we find that the localized spoof surface plasmon polariton has a significant toroidal dipole moment, which is responsible for the high Q factor, as well as an electric quadrupole moment. In addition, the dispersion properties of spoof surface plasmon polaritons are analyzed using a modal expansion method and numerical calculations

Website Usability: A Re-Examination through the Lenses of ISO Standards

The original conceptualization of usability was ease of use, this was later expanded into a multi-dimensional construct in ISO standards and usability literature. Such an expansion is seen as an improvement, since cross-study comparison or benchmarking cannot objectively be done without a common set of usability components being defined. The current issue lies in how these components are operationalized, measured and validated. Although ISO standards ties usability to contextual situations, recent research has started to also recognize psychographic and demographic variations within the same context. The purpose of this study is to review web site usability as it relates to ISO standards (more specifically ISO 9126, ISO 9241 and ISO/IEC 25010) and existing usability studies. Implications for researchers and practitioners are provided

microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway

microRNA-29b (miR-29b) is known to be associated with TGF-β-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 induced-fibrogenesis, concomitant with decreased expression of α-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3'UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed α-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b.published_or_final_versio

Breakdown and recovery in traffic flow models

Most car-following models show a transition from laminar to ``congested'' flow and vice versa. Deterministic models often have a density range where a disturbance needs a sufficiently large critical amplitude to move the flow from the laminar into the congested phase. In stochastic models, it may be assumed that the size of this amplitude gets translated into a waiting time, i.e.\ until fluctuations sufficiently add up to trigger the transition. A recently introduced model of traffic flow however does not show this behavior: in the density regime where the jam solution co-exists with the high-flow state, the intrinsic stochasticity of the model is not sufficient to cause a transition into the jammed regime, at least not within relevant time scales. In addition, models can be differentiated by the stability of the outflow interface. We demonstrate that this additional criterion is not related to the stability of the flow. The combination of these criteria makes it possible to characterize commonalities and differences between many existing models for traffic in a new way

Perineo-penile Degloving Exposure in Quartey's Urethroplasty: A Preliminary Report

Objective: To present a technique of stricture exposure in Quartey's urethroplasty. Methods: A retrospective analysis of case files of seven patients that underwent perineo-penile degloving (PPD) exposure for Quartey's urethroplasty was done and formed the basis of this communication.The perineo-penile degloving exposure involves a midline perineal incision to expose the bulbar urethral and a circumcising incision to deglove the penis which is later delivered to the perineum through the retro-scrotal tunnel. The urethroplasty is then done in a single operation field. Results: Seven patients with long segment urethra stricture were repaired using PPD exposure during the study period. The age ranged from 35 to 70 years with a mean of 48.6±11.1 years. The peno-bulbar site was involved in six (85.7%) of the patients. The mean intra-operative length of the stricture is 7.6±1.5cm. All the patients had Quartey's flap for their reconstruction under spinal anaesthesia with mean operation time of 3.16±0.50 hours (range 2.30 – 4.00 hours). They all had ventral on-lay repair except for one patient who had tubularization of the flap and anastomosis. Three of the patients had excellent short-term outcome. However, one patient developed slight distal penile skin necrosis, two patients had perineal wound infection and one patient could not void despite patent urethra postoperatively. Of the patients, only one had extravasation of contrast on pericatheter urethrogram which warranted leaving the urethral catheter for one more week. The mean follow-up period was 8.3±4.5 months with a range of 3 to 14 months. There has being no evidence of recurrence clinically or urodynamically thus far. Conclusion: PPD is convenient and allows tension-free, water-tight reconstruction in a single operation field with a comparable short-term outcome. Key words: urethral stricture, Quartey's urethroplasty, perineo-penile degloving, exposure