GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

Twitter as a technology for audiencing and fandom : the #Eurovision phenomenon

Amongst the most prominent uses of Twitter at present is its role in the discussion of widely televised events: Twitter’s own statistics for 2011, for example, list major entertainment spectacles (the MTV Music Awards, the BET Awards) and sports matches (the UEFA Champions League final, the FIFA Women’s World Cup final) amongst the events generating the most tweets per second during the year (Twitter, 2011). User activities during such televised events constitute a specific, unique category of Twitter use, which differs clearly from the other major events which generate a high rate of tweets per second (such as crises and breaking news, from the Japanese earthquake and tsunami to the death of Steve Jobs), as preliminary research has shown. During such major media events, by contrast, Twitter is used most predominantly as a technology of fandom instead: it serves in the first place as a backchannel to television and other streaming audiovisual media, enabling users offer their own running commentary on the universally shared media text of the event broadcast as it unfolds live. Centrally, this communion of fans around the shared text is facilitated by the use of Twitter hashtags – unifying textual markers which are now often promoted to prospective audiences by the broadcasters well in advance of the live event itself. This paper examines the use of Twitter as a technology for the expression of shared fandom in the context of a major, internationally televised annual media event: the Eurovision Song Contest. It constitutes a highly publicised, highly choreographed media spectacle whose eventual outcomes are unknown ahead of time and attracts a diverse international audience. Our analysis draws on comprehensive datasets for the ‘official’ event hashtags, #eurovision, #esc, and #sbseurovision. Using innovative methods which combine qualitative and quantitative approaches to the analysis of Twitter datasets containing several hundreds of thousands, we examine overall patterns of participation to discover how audiences express their fandom throughout the event. Minute-by-minute tracking of Twitter activity during the live broadcasts enables us to identify the most resonant moments during each event; we also examine the networks of interaction between participants to detect thematically or geographically determined clusters of interaction, and to identify the most visible and influential participants in each network. Such analysis is able to provide a unique insight into the use of Twitter as a technology for fandom and for what in cultural studies research is called ‘audiencing’: the public performance of belonging to the distributed audience for a shared media event. Our work thus contributes to the examination of fandom practices led by Henry Jenkins (2006) and other scholars, and points to Twitter as an important new medium facilitating the connection and communion of such fans.

The Cambridge companion to creative writing [Edited book]

Creative writing has become a highly professionalised academic discipline, with popular courses and prestigious degree programmes worldwide. This book is a must for all students and teachers of creative writing, indeed for anyone who aspires to be a published writer. It engages with a complex art in an accessible manner, addressing concepts important to the rapidly growing field of creative writing, while maintaining a strong craft emphasis, analysing exemplary models of writing and providing related writing exercises. Written by professional writers and teachers of writing, the chapters deal with specific genres or forms – ranging from the novel to new media – or with significant topics that explore the cutting edge state of creative writing internationally (including creative writing and science, contemporary publishing and new workshop approaches).

Life writing

Two hundred years ago life writing was already highly popular in the form of autobiography, memoir, biography, journals, essays and diaries. It now commands a huge share of the publishing market, as there is an enormous demand from readers for narratives based directly on 'real lives'. There is a lot of common ground between the two main forms - autobiography/memoir and biography: both require skilled storytelling [rather than listing facts and events], research and imagination. The quality of the writing itself is crucial to the impact on the reader. A person can have an existing, worthy life but unfortunately write about it (or be written about) in a dull way. And how a person is remembered and valued can be a factor of life writing about or by them. This chapter will define and contextualise life writing, look at specific detailed examples, and offer guidance on how to write effectively.

Recipe for success : cooking up a storm in the technology classroom

Ingredients: - 1 cup Vision - 100ml ‘Real World’ Application - 100ml Unit Structure/Organisation - 100ml Student-centric Approach [optional: Add Social Media/Popular Culture for extra goodness] - Large Dollop of Passion + Enthusiasm - Sprinkle of Approachability Mix all ingredients well. Cover and leave to rise in a Lecture Theatre for 1.5 hours. Cook in a Classroom for 1.5 hours. Garnish with a dash of Humour before serving. Serves 170 Students

Sunlight and other determinants of circulating 25-hydroxyvitamin D levels in black and white participants in a nationwide U.S. study

Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n 842), blacks (n 646), and people of other races/ethnicities (n 12). Participants were recruited monthly (20082009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25 of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.

Review : "Networking : commercial television in Australia : a history" -- Nick Herd

Nick Herd begins his institutional history of Australian commercial television in the early 1890s, when an amateur inventor named Henry Sutton designed the ‘telephane’ with the intent of watching the Melbourne Cup in his home town of Ballarat. The ‘race that stops a nation’ was not broadcast live on television until 1960, but Sutton’s initiative indicates how closely sport and television were aligned in Australia even before the medium existed. The first licensed commercial stations to begin regular broadcasting went on air in Sydney and Melbourne shortly before the 1956 Melbourne Olympic Games, although Herd claims that this was ‘almost accidental’ rather than planned. (49) Only Melbourne viewers were able to see some events live, many via television sets in Ampol service stations following the company’s last minute sponsorship of coverage on Melbourne station GTV-9...

Decision making under pressure : a behavioural economics perspective

This research investigates the decision making process of individuals from revealed preferences in extreme environments or life-and-death situations, from a behavioral economics perspective. The empirical analysis of revealed behavioral preferences shows how the individual decision making process can deviate from the standard self-interested or “homo economicus” model in non-standard situations. The environments examined include: elite athletes in FIFA World and Euro Cups; climbing on Everest and the Himalaya; communication during 9/11 and risk seeking after the 2011 Brisbane floods. The results reveal that the interaction of culture and environment has a significant impact on the decision process, as social behaviors and institutions are intimately intertwined, which govern the processes of human behavior and interaction. Additionally, that risk attitudes are not set and that immediate environmental factors can induce a significant shift in an individuals risk seeking behaviors.

Primary stability of two uncemented acetabular components of different geometry : hemispherical or peripherally enhanced?

Objective This study compared the primary stability of two commercially available acetabular components from the same manufacturer, which differ only in geometry; a hemispherical and a peripherally enhanced design (peripheral self-locking (PSL)). The objective was to determine whether altered geometry resulted in better primary stability. Methods Acetabular components were seated with 0.8 mm to 2 mm interference fits in reamed polyethylene bone substrate of two different densities (0.22 g/cm3 and 0.45 g/cm3). The primary stability of each component design was investigated by measuring the peak failure load during uniaxial pull-out and tangential lever-out tests. Results There was no statistically significant difference in seating force (p = 0.104) or primary stability (pull-out p = 0.171, lever-out p = 0.087) of the two components in the low-density substrate. Similarly, in the high-density substrate, there was no statistically significant difference in the peak pull-out force (p = 0.154) or lever-out moment (p = 0.574) between the designs. However, the PSL component required a significantly higher seating force thanthe hemispherical cup in the high-density bone analogue (p = 0.006). Conclusions Higher seating forces associated with the PSL design may result in inadequate seating and increased risk of component malpositioning or acetabular fracture in the intra-operative setting in high-density bone stock. Our results, if translated clinically, suggest that a purely hemispherical geometry may have an advantage over a peripherally enhanced geometry in high density bone stock.

Swimmer localization from a moving camera

At the highest level of competitive sport, nearly all performances of athletes (both training and competitive) are chronicled using video. Video is then often viewed by expert coaches/analysts who then manually label important performance indicators to gauge performance. Stroke-rate and pacing are important performance measures in swimming, and these are previously digitised manually by a human. This is problematic as annotating large volumes of video can be costly, and time-consuming. Further, since it is difficult to accurately estimate the position of the swimmer at each frame, measures such as stroke rate are generally aggregated over an entire swimming lap. Vision-based techniques which can automatically, objectively and reliably track the swimmer and their location can potentially solve these issues and allow for large-scale analysis of a swimmer across many videos. However, the aquatic environment is challenging due to fluctuations in scene from splashes, reflections and because swimmers are frequently submerged at different points in a race. In this paper, we temporally segment races into distinct and sequential states, and propose a multimodal approach which employs individual detectors tuned to each race state. Our approach allows the swimmer to be located and tracked smoothly in each frame despite a diverse range of constraints. We test our approach on a video dataset compiled at the 2012 Australian Short Course Swimming Championships.

Results using Trabecular Metal™ augments in combination with acetabular impaction bone grafting in deficient acetabula

We examined whether the use of trabecular metal wedges to fill segmental defects is an effective method of socket reconstruction when used in combination with impaction grafting and implantation of a cemented socket. Fifteen hips in 14 patients underwent impaction grafting in combination with a TM wedge with a minimum of 2 years follow-up. All patients had their defects assessed using the Paprosky classification. Patients were reviewed with x-rays and migration of the implant was measured. Outcome scores were also collected. Mean follow-up was 39 months (25-83). The mean age at surgery was 67.8 (49-85) years. Seven of the patients had previously undergone impaction grafting with the use of a stainless steel rim mesh to constrain the graft. None of the patients had failed either clinically or radiologically.

Breastfeeding self-efficacy of women using second-line strategies for healthy term infants in the first week postpartum : an Australian observational study

Background Breastfeeding self-efficacy (BFSE) supports breastfeeding initiation and duration. Challenges to breastfeeding may undermine BFSE, but second-line strategies including nipple shields, syringe, cup, supply line and bottle feeding may support breastfeeding until challenges are resolved. The primary aim of this study was to examine BFSE in a sample of women using second-line strategies for feeding healthy term infants in the first week postpartum. Methods A retrospective self-report study was conducted using the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), demographic and infant feeding questionnaires. Breastfeeding women who gave birth to a singleton healthy term infant at one private metropolitan birthing facility in Australia from November 2008 to February 2009 returned anonymous questionnaires by mail. Results A total of 128 (73 multiparous, 55 primiparous) women participated in the study. The mean BSES-SF score was 51.18 (Standard deviation, SD: 12.48). The median BSES-SF score was 53. Of women using a second-line strategy, 16 exceeded the median, and 42 were below. Analyses using Kruskal-Wallis tests confirmed this difference was statistically significant (H = 21.569, p = 0.001). The rate of second-line strategy use was 48%. The four most commonly used second-line strategies were: bottles with regular teats (77%); syringe feeding (44%); bottles with wide teats (34%); and nipple shields (27%). Seven key challenges were identified that contributed to the decision to use second-line strategies, including: nipple pain (40%); unsettled infant (40%); insufficient milk supply (37%); fatigue (37%); night nursery care (25%); infant weight loss > 10% (24%); and maternal birth associated pain (20%). Skin-to-skin contact at birth was commonly reported (93%). At seven days postpartum 124 women (97%) were continuing to breastfeed. Conclusions The high rate of use of second-line strategies identified in this study and high rate of breastfeeding at day seven despite lower BFSE indicate that such practices should not be overlooked by health professionals. The design of this study does not enable determination of cause-effect relationships to identify factors which contribute to use of second-line strategies. Nevertheless, the significantly lower BSES-SF score of women using a second-line strategy highlights this group of women have particular needs that require attention.

Exploring the boundary between the siphon and barometer in a hypobaric chamber

Siphons have been used since ancient times, but exactly how they work is still a matter of debate. In order to elucidate the modus operandi of a siphon, a 1.5 m high siphon was set up in a hypobaric chamber to explore siphon behaviour in a low-pressure environment. When the pressure in the chamber was reduced to about 0.18 atmospheres, a curious waterfall-like feature appeared downstream from the apex of the siphon. A hypothesis is presented to explain the waterfall phenomenon. When the pressure was reduced further the siphon broke into two columns - in effect becoming two back-to-back barometers. This experiment demonstrates the role of atmospheric pressure in explaining the hydrostatic characteristics of a siphon and the role of molecular cohesion in explaining the hydrodynamic aspects.

Management of periprosthetic joint infection after total hip arthroplasty using a Custom Made Articulating Spacer (CUMARS); the exeter experience

Periprosthetic joint infection (PJI) after THA is a major complication with an incidence of 1-3%. We report our experiences with a technique using a custom-made articulating spacer (CUMARS) at the first of two-stage treatment for PJI. This technique uses widely available all-polyethylene acetabular components and the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy-six hips were treated for PJI using this technique. Performed as the first of a two-stage procedure, good functional results were commonly seen, leading to postponing second stage indefinitely with retention of the CUMARS prosthesis in 34 patients. The CUMARS technique presents an alternative to conventional spacers, using readily available components that are well tolerated, allowing weight bearing and mobility, and achieving comparable eradication rates.

An experimental based assessment of the deviation of the bearing characteristic frequencies

Slippage in the contact roller-races has always played a central role in the field of diagnostics of rolling element bearings. Due to this phenomenon, vibrations triggered by a localized damage are not strictly periodic and therefore not detectable by means of common spectral functions as power spectral density or discrete Fourier transform. Due to the strong second order cyclostationary component, characterizing these signals, techniques such as cyclic coherence, its integrated form and square envelope spectrum have proven to be effective in a wide range of applications. An expert user can easily identify a damage and its location within the bearing components by looking for particular patterns of peaks in the output of the selected cyclostationary tool. These peaks will be found in the neighborhood of specific frequencies, that can be calculated in advance as functions of the geometrical features of the bearing itself. Unfortunately the non-periodicity of the vibration signal is not the only consequence of the slippage: often it also involves a displacement of the damage characteristic peaks from the theoretically expected frequencies. This issue becomes particularly important in the attempt to develop highly automated algorithms for bearing damage recognition, and, in order to correctly set thresholds and tolerances, a quantitative description of the magnitude of the above mentioned deviations is needed. This paper is aimed at identifying the dependency of the deviations on the different operating conditions. This has been possible thanks to an extended experimental activity performed on a full scale bearing test rig, able to reproduce realistically the operating and environmental conditions typical of an industrial high power electric motor and gearbox. The importance of load will be investigated in detail for different bearing damages. Finally some guidelines on how to cope with such deviations will be given, accordingly to the expertise obtained in the experimental activity.