In Vitro and In Vivo Evaluation of Novel Ciprofloxacin-Releasing Silicone Hydrogel Contact Lenses

Hui, A., Willcox, M., & Jones, L. (2014). In Vitro and In Vivo Evaluation of Novel Ciprofloxacin-Releasing Silicone Hydrogel Contact Lenses. Investigative Opthalmology & Visual Science, 55(8), 4896. https://doi.org/10.1167/iovs.14-14855Purpose.: The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. Methods.: Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. Results.: Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). Conclusions.: These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis.Supported by the Natural Science and Engineering Research Council of Canada (NSERC)20/20 Network for the Development of Advanced Ophthalmic Materialsand by an NSERC Alexander Graham Bell Doctoral Scholarshipthe Ezell Fellowship from the American Optometric Foundationand the Endeavour Research Grant from the Australian Government (AH)

Peak reduction technique in commutative algebra

The "peak reduction" method is a powerful combinatorial technique with applications in many different areas of mathematics as well as theoretical computer science. It was introduced by Whitehead, a famous topologist and group theorist, who used it to solve an important algorithmic problem concerning automorphisms of a free group. Since then, this method was used to solve numerous problems in group theory, topology, combinatorics, and probably in some other areas as well. In this paper, we give a survey of what seems to be the first applications of the peak reduction technique in commutative algebra and affine algebraic geometry.Comment: survey; 10 page

Free subgroups of one-relator relative presentations

Suppose that G is a nontrivial torsion-free group and w is a word over the alphabet G\cup\{x_1^{\pm1},...,x_n^{\pm1}\}. It is proved that for n\ge2 the group \~G= always contains a nonabelian free subgroup. For n=1 the question about the existence of nonabelian free subgroups in \~G is answered completely in the unimodular case (i.e., when the exponent sum of x_1 in w is one). Some generalisations of these results are discussed.Comment: V3: A small correction in the last phrase of the proof of Theorem 1. 4 page

The TFOS International Workshop on Contact Lens Discomfort: Introduction

Nichols, J. J., Jones, L., Nelson, J. D., Stapleton, F., Sullivan, D. A., & Willcox, M. D. P. (2013). The TFOS International Workshop on Contact Lens Discomfort: Introduction. Investigative Opthalmology & Visual Science, 54(11), TFOS1. https://doi.org/10.1167/iovs.13-13195For many years, the contact lens field had focused on safety associated with contact lens wear—and for good reason, given the lack of understanding of the risk factors and etiology of serious complications such as microbial keratitis. However, as knowledge came to light on these complications through the 1980s and 1990s, it allowed for practitioners to become more comfortable managing these complications, along with the introduction of products that helped reduce or prevent some of these problems. It was during this time, beginning in the mid-1980s, that the field itself became cognizant of the issues associated with comfort, or discomfort, during contact lens wear. Since that time, we have witnessed the field (and industry) shift its attention toward understanding the issue of contact lens discomfort (CLD). Contact lens discomfort is a substantial and burdensome problem experienced frequently by contact lens wearers. It is well established that most contact lens wearers experience CLD, at least occasionally, although many experience CLD to such a severity that they feel compelled to alter their wearing habits. Common, although palliative at best, treatments include the periodic use of rewetting drops, contact lens removal, contact lens refitting (using different lens designs or materials or replacement schedules), and changes in the contact lens care solutions or regimens, in addition to other less commonly used approaches including topical or systemic medications, alterations in diet, and punctal plugs. Ultimately, CLD is the primary factor associated with permanent discontinuation from contact lens wear. Given the importance of the issue of CLD to both patients and practitioners alike, the time was right to move the field forward by taking steps to bring global consensus to our current understanding of this condition.Supported by unrestricted financial support from Alcon (title sponsor), Allergan, Bausch & Lomb, Santen, Menicon, Vistakon, Laboratoires Théa, Optima, Oculus, CooperVision, and Contact Lens Spectrum

Earth pressure on cantilever walls at design retained heights

There are many methods for the analysis and design of embedded cantilever retaining walls. They involve various different simplifications of the pressure distribution to allow calculation of the limiting equilibrium retained height and the bending moment when the retained height is less than the limiting equilibrium value, i.e. the serviceability case. Recently, a new method for determining the serviceability earth pressure and bending moment has been proposed. This method makes an assumption defining the point of zero net pressure. This assumption implies that the passive pressure is not fully mobilised immediately below the excavation level. The finite element analyses presented in this paper examine the net pressure distribution on walls in which the retained height is less, than the limiting equilibrium value. The study shows that for all practical walls, the earth pressure distributions on the front and back of the wall are at their limit values, Kp and K-a respectively, when the lumped factor of safety F-r is less than or equal to2.0. A rectilinear net pressure distribution is proposed that is intuitively logical. It produces good predictions of the complete bending moment diagram for walls in the service configuration and the proposed method gives results that have excellent agreement with centrifuge model tests. The study shows that the method for determining the serviceability bending moment suggested by Padfield and Mair(1) in the CIRIA Report 104 gives excellent predictions of the maximum bending moment in practical cantilever walls. It provides the missing data that have been needed to verify and justify the CIRIA 104 method

Economical adjunction of square roots to groups

How large must an overgroup of a given group be in order to contain a square root of any element of the initial group? We give an almost exact answer to this question (the obtained estimate is at most twice worse than the best possible) and state several related open questions.Comment: 5 pages. A Russian version of this paper is at http://mech.math.msu.su/department/algebra/staff/klyachko/papers.htm V2: minor correction

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Jekyll and Hyde: men's constructions of feminism and feminists

Research and commentary on men's responses to feminism has demonstrated the range of ways in which men have mobilised both against and for feminist principles. This paper argues that further analyses of men's responses require a sophisticated theory of discourse acknowledging the fragmented and contradictory nature of representation. A corpus of men's talk on feminism and feminists was studied to identify the pervasive patterns in men's accounting and regularities in rhetorical organisation. Material from two samples of men was included: a sample of white middle-class 17-18 year old school students and a sample of 60 interviews with a more diverse sample of older men aged 20 to 64. Two interpretative repertoires of feminism and feminists were identified. These set up a 'Jekyll and Hyde' binary and positioned feminism along with feminists very differently as reasonable versus extreme and monstrous. Both repertoires tended to be deployed together and the paper explores the ideological and interactional consequences of typical deployments along with the identity work accomplished by the men as they positioned themselves in relation to these

Nearest Neighbor Distances on a Circle: Multidimensional Case

We study the distances, called spacings, between pairs of neighboring energy levels for the quantum harmonic oscillator. Specifically, we consider all energy levels falling between E and E+1, and study how the spacings between these levels change for various choices of E, particularly when E goes to infinity. Primarily, we study the case in which the spring constant is a badly approximable vector. We first give the proof by Boshernitzan-Dyson that the number of distinct spacings has a uniform bound independent of E. Then, if the spring constant has components forming a basis of an algebraic number field, we show that, when normalized up to a unit, the spacings are from a finite set. Moreover, in the specific case that the field has one fundamental unit, the probability distribution of these spacings behaves quasiperiodically in log E. We conclude by studying the spacings in the case that the spring constant is not badly approximable, providing examples for which the number of distinct spacings is unbounded.Comment: Version 2 is updated to include more discussion of previous works. 17 pages with five figures. To appear in the Journal of Statistical Physic