An international survey of toric contact lens prescribing

Objectives To characterize toric contact lens prescribing worldwide. Methods Up to 1,000 survey forms were sent to contact lens fitters in up to 39 countries between January and March every year for 5 consecutive years (2007–2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Only data for toric and spherical soft lens fits were analyzed. Survey data collected since 1996 were also analyzed for 7 nations to assess toric lens fitting trends since that time. Results Data were collected in relation to 21,150 toric fits (25%) and 62,150 spherical fits (75%). Toric prescribing ranged from 6% of lenses in Russia to 48% in Portugal. Compared with spherical fittings, toric fittings can be characterized as follows: older age (29.8 ± 11.4 years vs. 27.6 ± 10.8 years for spherical lenses); men are overrepresented (38% vs. 34%); greater proportion of new fits (39% vs. 32%); use of silicone hydrogel lenses (49% vs. 39%); and lower proportion of daily disposable lenses (14% vs. 28%). There has been a continuous increase in toric lens prescribing between 1996 and 2011. The proportion of toric lens fits was positively related to the gross domestic product at purchasing power parity per capita for year 2011 (r2 = 0.21; P=0.004). Conclusions At the present time, in the majority of countries surveyed, toric soft contact lens prescribing falls short of that required to correct clinically significant astigmatism (≥0.75 diopters) in all lens wearers.

Determinants of the frequency of contact lens wear

Objectives To characterize and discover the determinants of the frequency of wear (FOW) of contact lenses. Methods Survey forms were sent to contact lens fitters in up to 40 countries between January and March every year for 5 consecutive years (2007–2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Only data for daily wear lens fits were analyzed. Results Data were collected in relation to 74,510 and 9,014 soft and rigid lens fits, respectively. Overall, FOW was 5.9±1.7 days per week (DPW). When considering the proportion of lenses worn between one to seven DPW, the distribution for rigid lenses is skewed toward full-time wear (7 DPW), whereas the distribution for soft daily disposable lenses is perhaps bimodal, with large and small peaks at seven and two DPW, respectively. There is a significant variation in FOW among nations (P<0.0001), ranging from 6.8±1.0 DPW in Greece to 5.1±2.5 DPW in Kuwait. For soft lenses, FOW increases with decreasing age. Females (6.0±1.6 DPW) wear lenses more frequently than males (5.8±1.7 DPW) (P=0.0002). FOW is greater among those wearing presbyopic corrections (6.1±1.4 DPW) compared with spherical (5.9±1.7 DPW) and toric (5.9±1.6 DPW) designs (P<0.0001). FOW with hydrogel peroxide systems (6.4±1.1 DPW) was greater than that with multipurpose systems (6.2±1.3 DPW) (P<0.0001). Conclusions Numerous demographic and contact lens–related factors impact FOW. There may be a future trend toward a lower FOW associated with the increasing popularity of daily disposable lenses.

Observation of solution-induced corneal staining with fluorescein, rose bengal and lissamine green

Ever since sodium fluorescein (‘fluorescein’ [FL]) was first used to investigate the ocular surface over a century ago, the term ‘staining’ has been taken to mean the presence of ocular surface fluorescence [1]. This term has not been necessarily taken to infer any particular mechanism of causation, and indeed, can be attributed to a variety of possible aetiologies [2]. In recent times, there has been considerable interest in a form of ocular surface fluorescence seen in association with the use of certain combinations of soft contact lenses and multipurpose solutions. The first clinical account of this phenomenon was reported by Jones et al. [3], which was followed by a more formal investigation by the same author in 2002 [4]. Jones et al described this appearance as a ‘classic solution-based toxicity reaction’. Subsequently, this appearance has come to be known as ‘solution-induced corneal staining’ or more recently by the acronym ‘SICS’ [5]. The term SICS is potentially problematic in that from a cell biology point of view, there is an inference that ‘staining’ means the entry of a dye into corneal epithelial cells. Morgan and Maldonado-Codina [2] noted there was no foundation of solid scientific literature underpinning our understanding of the true basic causative mechanisms of this phenomenon; since that time, further work has been published in this field [6] and [7] but questions still remain about the precise aetiology of this phenomenon...

Book review: 'The Cornea' edited by H.E. Kaufman, B.A. Baron, M.B. McDonald and S.R. Waltman.

Parsons' Diseases of the Eye, first published in 1907, is one of the foundation texts of modern ophthalmology. It has seen a new edition at approximately 5-year intervals throughout the century. This latest edition incorporates developments that have taken place within the specialty since the 1984 impression, but remains in a virtually unchanged format...

International contact lens prescribing in 2011

This is the 11th annual report of contact lens prescribing trends that we have prepared for Contact Lens Spectrum. Each year, we capture current modes of contact lens practice by asking practitioners in each market (optometrists, opticians or ophthalmologists, as appropriate) to provide information about the first 10 lens fits undertaken after receiving our paper or electronic survey form. In 2011, we captured information about 22,362 fits in 29 countries.

Targeting nuclear factor-kappa B to overcome resistance to chemotherapy

Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-κB pathway. NF-κB is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.

Distinguishing between mechanisms of cell aggregation using pair-correlation functions

Many cell types form clumps or aggregates when cultured in vitro through a variety of mechanisms including rapid cell proliferation, chemotaxis, or direct cell-to-cell contact. In this paper we develop an agent-based model to explore the formation of aggregates in cultures where cells are initially distributed uniformly, at random, on a two-dimensional substrate. Our model includes unbiased random cell motion, together with two mechanisms which can produce cell aggregates: (i) rapid cell proliferation, and (ii) a biased cell motility mechanism where cells can sense other cells within a finite range, and will tend to move towards areas with higher numbers of cells. We then introduce a pair-correlation function which allows us to quantify aspects of the spatial patterns produced by our agent-based model. In particular, these pair-correlation functions are able to detect differences between domains populated uniformly at random (i.e. at the exclusion complete spatial randomness (ECSR) state) and those where the proliferation and biased motion rules have been employed - even when such differences are not obvious to the naked eye. The pair-correlation function can also detect the emergence of a characteristic inter-aggregate distance which occurs when the biased motion mechanism is dominant, and is not observed when cell proliferation is the main mechanism of aggregate formation. This suggests that applying the pair-correlation function to experimental images of cell aggregates may provide information about the mechanism associated with observed aggregates. As a proof of concept, we perform such analysis for images of cancer cell aggregates, which are known to be associated with rapid proliferation. The results of our analysis are consistent with the predictions of the proliferation-based simulations, which supports the potential usefulness of pair correlation functions for providing insight into the mechanisms of aggregate formation.

Towards consonance in urban form

By presenting the past as a repository of the characteristics of urban formation, urban morphology utilizes a knowledge platform as the basis for interpretation of accordant architectural responses (Levy, 1999). Operating within this framework at the scale of architectural features of individual buildings, and imbued with reference to the intrinsic architectural elements of both preceding and existing building forms, micro-morphology (Larkham, 2006, p. 126) provides the efficacy for new architecture that emerges from such a manner of composition...

Mechanism based emulation of dynamic simulation models : concept and application in hydrology

Many model-based investigation techniques, such as sensitivity analysis, optimization, and statistical inference, require a large number of model evaluations to be performed at different input and/or parameter values. This limits the application of these techniques to models that can be implemented in computationally efficient computer codes. Emulators, by providing efficient interpolation between outputs of deterministic simulation models, can considerably extend the field of applicability of such computationally demanding techniques. So far, the dominant techniques for developing emulators have been priors in the form of Gaussian stochastic processes (GASP) that were conditioned with a design data set of inputs and corresponding model outputs. In the context of dynamic models, this approach has two essential disadvantages: (i) these emulators do not consider our knowledge of the structure of the model, and (ii) they run into numerical difficulties if there are a large number of closely spaced input points as is often the case in the time dimension of dynamic models. To address both of these problems, a new concept of developing emulators for dynamic models is proposed. This concept is based on a prior that combines a simplified linear state space model of the temporal evolution of the dynamic model with Gaussian stochastic processes for the innovation terms as functions of model parameters and/or inputs. These innovation terms are intended to correct the error of the linear model at each output step. Conditioning this prior to the design data set is done by Kalman smoothing. This leads to an efficient emulator that, due to the consideration of our knowledge about dominant mechanisms built into the simulation model, can be expected to outperform purely statistical emulators at least in cases in which the design data set is small. The feasibility and potential difficulties of the proposed approach are demonstrated by the application to a simple hydrological model.

Hydroxyl radical formation in the gas phase oxidation of distonic 2-methylphenyl radical cations

The reactions of distonic 4-(N, N, N-trimethylammonium)-2-methylphenyl and 5-(N, N, N-trimethylammonium)-2-methylphenyl radical cations (m/z 149) with O-2 are studied in the gas phase using ion-trap mass spectrometry. Photodissociation (PD) of halogenated precursors gives rise to the target distonic charge-tagged methylphenyl radical whereas collision-induced dissociation (CID) is found to produce unreactive radical ions. The PD generated distonic radicals, however, react rapidly with O-2 to form \[M + O2](center dot+) and \[M + O-2 - OH](center dot+) ions, detected at m/z 181 and m/z 164, respectively. Quantum chemical calculations using G3SX(MP3) and M06-2X theories are deployed to examine key decomposition pathways of the 5-(N, N, N-trimethylammonium)-2-methylphenylperoxyl radical and rationalise the observed product ions. The prevailing product mechanism involves a 1,5- H shift in the peroxyl radical forming a QOOH-type intermediate that subsequently eliminates (OH)-O-center dot to yield charge-tagged 2-quinone methide. Our study suggests that the analogous process should occur for the neutral methylphenyl + O-2 reaction, thus serving as a plausible source of (OH)-O-center dot radicals in combustion environments. Grants: ARC/DP0986738, ARC/DP130100862

Formation and Fragmentation of Unsaturated Fatty Acid M-2H+Na (-) Ions: Stabilized Carbanions for Charge-Directed Fragmentation

Fatty acids are long-chain carboxylic acids that readily produce \[M - H](-) ions upon negative ion electrospray ionization (ESI) and cationic complexes with alkali, alkaline earth, and transition metals in positive ion ESI. In contrast, only one anionic monomeric fatty acid-metal ion complex has been reported in the literature, namely \[M - 2H + (FeCl)-Cl-II](-). In this manuscript, we present two methods to form anionic unsaturated fatty acid-sodium ion complexes (i.e., \[M - 2H + Na](-)). We find that these ions may be generated efficiently by two distinct methods: (1) negative ion ESI of a methanolic solution containing the fatty acid and sodium fluoride forming an \[M - H + NaF](-) ion. Subsequent collision-induced dissociation (CID) results in the desired \[M - 2H + Na](-) ion via the neutral loss of HF. (2) Direct formation of the \[M - 2H + Na](-) ion by negative ion ESI of a methanolic solution containing the fatty acid and sodium hydroxide or bicarbonate. In addition to deprotonation of the carboxylic acid moiety, formation of \[M - 2H + Na](-) ions requires the removal of a proton from the fatty acid acyl chain. We propose that this deprotonation occurs at the bis-allylic position(s) of polyunsaturated fatty acids resulting in the formation of a resonance-stabilized carbanion. This proposal is supported by ab initio calculations, which reveal that removal of a proton from the bis-allylic position, followed by neutral loss of HX (where X = F- and -OH), is the lowest energy dissociation pathway.

A spatial-indexing model for measuring neighbourhood-level land-use and transport integration

Significant attention has been given in urban policy literature to the integration of land-use and transport planning and policies—with a view to curbing sprawling urban form and diminishing externalities associated with car-dependent travel patterns. By taking land-use and transport interaction into account, this debate mainly focuses on how a successful integration can contribute to societal well-being, providing efficient and balanced economic growth while accomplishing the goal of developing sustainable urban environments and communities. The integration is also a focal theme of contemporary urban development models, such as smart growth, liveable neighbourhoods, and new urbanism. Even though available planning policy options for ameliorating urban form and transport-related externalities have matured—owing to growing research and practice worldwide—there remains a lack of suitable evaluation models to reflect on the current status of urban form and travel problems or on the success of implemented integration policies. In this study we explore the applicability of indicator-based spatial indexing to assess land-use and transport integration at the neighbourhood level. For this, a spatial index is developed by a number of indicators compiled from international studies and trialled in Gold Coast, Queensland, Australia. The results of this modelling study reveal that it is possible to propose an effective metric to determine the success level of city plans considering their sustainability performance via composite indicator methodology. The model proved useful in demarcating areas where planning intervention is applicable, and in identifying the most suitable locations for future urban development and plan amendments. Lastly, we integrate variance-based sensitivity analysis with the spatial indexing method, and discuss the applicability of the model in other urban contexts.

The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts

Heparan sulfate proteoglycans cooperate with basic fibroblast growth factor (bFGF/FGF2) signaling to control osteoblast growth and differentiation, as well as metabolic functions of osteoblasts. FGF2 signaling modulates the expression and activity of Runt-related transcription factor 2 (Runx2/Cbfa1), a key regulator of osteoblast proliferation and maturation. Here, we have characterized novel Runx2 target genes in osteoprogenitors under conditions that promote growth arrest while not yet permitting sustained phenotypic maturation. Runx2 enhances expression of genes related to proteoglycan-mediated signaling, including FGF receptors (e.g., FGFR2 and FGFR3) and proteoglycans (e.g., syndecans [Sdc1, Sdc2, Sdc3], glypicans [Gpc1], versican [Vcan]). Runx2 increases expression of the glycosyltransferase Exostosin-1 (Ext1) and heparanase, as well as alters the relative expression of N-linked sulfotransferases (Ndst1 = Ndst2 > Ndst3) and enzymes mediating O-linked sulfation of heparan sulfate (Hs2st > Hs6st) or chondroitin sulfate (Cs4st > Cs6st). Runx2 cooperates with FGF2 to induce expression of Sdc4 and the sulfatase Galns, but Runx2 and FGF2 suppress Gpc6, thus suggesting intricate Runx2 and FGF2 dependent changes in proteoglycan utilization. One functional consequence of Runx2 mediated modulations in proteoglycan-related gene expression is a change in the responsiveness of bone markers to FGF2 stimulation. Runx2 and FGF2 synergistically enhance osteopontin expression (>100 fold), while FGF2 blocks Runx2 induction of alkaline phosphatase. Our data suggest that Runx2 and the FGF/proteoglycan axis may form an extracellular matrix (ECM)-related regulatory feed-back loop that controls osteoblast proliferation and execution of the osteogenic program.