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.

Signal patterns of piston slap of a four-cylinder diesel engine

This paper presents an experimental study on the vibration signal patterns associated with a simulated piston slap test of a four-cylinder diesel engine. It is found that a simulated worn-off piston results in an increase in vibration RMS peak amplitudes associated with the major mechanical events of the corresponding cylinder (i.e., inlet and exhaust valve closing and combustion of Cylinder 1). This then led to an increase of overall vibration amplitude of the time domain statistical features such as RMS, Crest Factor, Skewness and Kurtosis in all loading conditions. The simulated worn-off piston not only increased the impact amplitude of piston slap during the engine combustion, it also produced a distinct impulse response during the air induction stroke of the cylinder attributing to an increase of lateral impact force as a result of piston reciprocating motion and the increased clearance between the worn-off piston and the cylinder. The unique signal patterns of piston slap disclosed in this paper can be utilized to assist in the development of condition monitoring tools for automated diagnosis of similar diesel engine faults in practical applications.

Encouraging, assisting and time to EAT : improved nutritional intake for older medical patients receiving Protected Mealtimes and/or additional nursing feeding assistance

Background & Aims: Inadequate feeding assistance and mealtime interruptions during hospitalisation may contribute to malnutrition and poor nutritional intake in older people. This study aimed to implement and compare three interventions designed to specifically address mealtime barriers and improve energy intakes of medical inpatients aged ≥65 years. Methods: Pre-post study compared three mealtime assistance interventions: PM: Protected Mealtimes with multidisciplinary education; AIN: additional assistant-in-nursing (AIN) with dedicated meal role; PM+AIN: combined intervention. Dietary intake of 254 patients (pre: n=115, post: n=141; mean age 80±8) was visually estimated on a single day in the first week of hospitalisation and compared with estimated energy requirements. Assistance activities were observed and recorded. Results: Mealtime assistance levels significantly increased in all interventions (p<0.01). Post-intervention participants were more likely to achieve adequate energy intake (OR=3.4, p=0.01), with no difference noted between interventions (p=0.29). Patients with cognitive impairment or feeding dependency appeared to gain substantial benefit from mealtime assistance interventions. Conclusions: Protected Mealtimes and additional AIN assistance (implemented alone or in combination) may produce modest improvements in nutritional intake. Targeted feeding assistance for certain patient groups holds promise; however, alternative strategies are required to address the complex problem of malnutrition in this population.

The children and sunscreen study : a crossover trial investigating children's sunscreen application thickness and the influence of age and dispenser type.

OBJECTIVES: To measure the thickness at which primary schoolchildren apply sunscreen on school day mornings and to compare it with the thickness (2.00 mg/cm(2)) at which sunscreen is tested during product development, as well as to investigate how application thickness was influenced by age of the child (school grades 1-7) and by dispenser type (500-mL pump, 125-mL squeeze bottle, or 50-mL roll-on). DESIGN: A crossover quasiexperimental study design comparing 3 sunscreen dispenser types. SETTING: Children aged 5 to 12 years from public primary schools (grades 1-7) in Queensland, Australia. PARTICIPANTS: Children (n=87) and their parents randomly recruited from the enrollment lists of 7 primary schools. Each child provided up to 3 observations (n=258). INTERVENTION: Children applied sunscreen during 3 consecutive school weeks (Monday through Friday) for the first application of the day using a different dispenser each week. MAIN OUTCOME MEASURE: Thickness of sunscreen application (in milligrams per square centimeter). The dispensers were weighed before and after use to calculate the weight of sunscreen applied. This was divided by the coverage area of application (in square centimeters), which was calculated by multiplying the children's body surface area by the percentage of the body covered with sunscreen. RESULTS: Children applied their sunscreen at a median thickness of 0.48 mg/cm(2). Children applied significantly more sunscreen when using the pump (0.75 mg/cm(2)) and the squeeze bottle (0.57 mg/cm(2)) compared with the roll-on (0.22 mg/cm(2)) (P<.001 for both). CONCLUSIONS: Regardless of age, primary schoolchildren apply sunscreen at substantially less than 1.00 mg/cm(2), similar to what has been observed among adults. Some sunscreen dispensers seem to facilitate thicker application than others.

Effect of Australia's walk to work day campaign on adults' active commuting and physical activity behavior

Purpose. To determine whether Australia's Walk to Work Day media campaign resulted in behavioural change among targeted groups. Methods. Pre- and postcampaign telephone surveys of a cohort of adults aged 18 to 65 years (n = 1100, 55% response rate) were randomly sampled from Australian major melropolitan areas. Tests for dependent samples were applied (McNemax chi(2) or paired t-test). Results. Among participants who did not usually actively commute to work was a significant decrease in car only use an increase in walking combined with public transport. Among those who were employed was a significant increase in total time walking (+16 min/wk; t [780] = 2.04, p < .05) and in other moderate physical activity (+120 min/wk; t [1087] = 4.76, p < .005), resulting in a significant decrease in the proportion who were inactive (chi(2) (1) = 6.1, p < .05). Conclusion. Although nonexperimental, the Walk to Work Day initiative elicited short-term changes in targeted behaviors among target groups. Reinforcement by integrating worksite health promotion strategies may be required for sustained effects.

Preservice teachers’ observations of their mentors’ teaching strategies for differentiated learning

Tensions exist between teacher-centred and learner-centred approaches with constructivism as being favoured for learning in the 21st Century. There is little evidence of teaching strategies being used in the field for differentiating student learning. In addition, preservice teachers need to learn about teaching strategies for which observations of their mentor teachers can provide practical applications. This study explores 16 preservice teachers’ observations of their mentors’ teaching strategies over a four-week professional experience. They provided a minimum of five written observations during this period. Findings indicated that these preservice teachers observed their mentors’ practices and recorded four key teaching strategies used to differentiate learning, namely: (1) designating facilitators for students’ learning, including teacher, peers, parents, and support staff such as teachers aides, (2) managing student groups, (3) contexts for learning, and (4) using a range of teaching aids (visual, auditory, games) and resources. Preservice teachers’ observations of their mentor teachers indicated that they can commence at early stages for identifying teaching strategies and how they work for differentiating student learning.

Constructing Technology Projects with Young Children : Four Detailed Case Studies of Mounting Constructivist Learning Projects Using Dimple Technologies for Young Children

The work by graduate teachers in this volume represent intentional design of learning experiences using technology for Early Childhood settings. They were given a two-part design task: a sequence of lessons organised around a themed project; and the collection of resources to support such activities. The project had to be constructive in nature where the children built objects and representations that were meaningful to them. The excellent works presented here offer a range of approaches that would be suitable in a variety of contexts. Because they are reasoned, these projects offer flexibility in implementation along with confidence that they would be effective.

Air pollution trends in four Australian cities

This study examined the long-term trends in four air pollutants in Australia’s four largest cities between 1996 and 2011. There were long-term improvements in carbon monoxide and sulfur dioxide. Particulate matter levels (PM10) remained relatively constant. Ozone levels increased in all four cities when including the influence of temperature, and levels are predicted to increase further because of climate change.

Subacute effects of ecstasy on mood : an exploration of associated risk factors

Ecstasy use may result in lowered mood, anxiety or aggression in the days following use. Yet, few studies have investigated what factors increase the risk of experiencing such symptoms. Ecstasy users (at least once in the last 12 months) who subsequently took ecstasy (n=35) over the next week, were compared on measures of mood, sleep, stress and drug use, with those who abstained (n=21) that week. Measures were administered the week prior to ecstasy use and 1 and 3 days following use, or the equivalent day for abstainers. Mood symptoms were assessed using the Kessler-10 self-report psychological distress scale, a subjective mood rating (1-10), and the depression, anxiety and hostility items of the clinician-rated Brief Psychiatric Rating Scale. Timeline followback methods were used to collect information on drug use and life stress in the past month. Self-reported sleep quality was also assessed. Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms. Rather, lowered mood and increased psychological distress were associated with self-reported hours and quality of sleep obtained during the 3-day follow up. These findings highlight the importance of considering sleep disruption in understanding the short-term mood effects of ecstasy use.

Realizing 'four comforts' in the urban fringe : the case of White Horse Lake Eco-creative City Project, Hangzhou, China

This article examines a cultural and creative industries park project – the White Horse Lake Ecocreative City on land outside the urban centre of Hangzhou, China, which uses an imaginary rural lifestyle as its key attraction. By analysing government policies and development plans, and through interviews with initiators, managers and creative practitioners, the article first assesses the geographical position, that is, the impact of locality with regard to both hard and soft infrastructure of the project; it then examines the synergies and tensions embedded in the strategic goals, that is, to build the right city for ‘four comforts’ (siyi, 四宜) – for residence, for business, for travel and for culture. The article concludes that Chinese-style cultural conversion remains locked in a top-down ideological framework, one that rural residents and the new ‘creative class’ are expected to respect.

Fatalism, superstition, religion, and culture : road user beliefs and behaviour in Pakistan

Road traffic crashes have emerged as a major health problem around the world. Road crash fatalities and injuries have been reduced significantly in developed countries, but they are still an issue in low and middle-income countries. The World Health Organization (WHO, 2009) estimates that the death toll from road crashes in low- and middle-income nations is more than 1 million people per year, or about 90% of the global road toll, even though these countries only account for 48% of the world's vehicles. Furthermore, it is estimated that approximately 265,000 people die every year in road crashes in South Asian countries and Pakistan stands out with 41,494 approximately deaths per year. Pakistan has the highest rate of fatalities per 100,000 population in the region and its road crash fatality rate of 25.3 per 100,000 population is more than three times that of Australia's. High numbers of road crashes not only cause pain and suffering to the population at large, but are also a serious drain on the country's economy, which Pakistan can ill-afford. Most studies identify human factors as the main set of contributing factors to road crashes, well ahead of road environment and vehicle factors. In developing countries especially, attention and resources are required in order to improve things such as vehicle roadworthiness and poor road infrastructure. However, attention to human factors is also critical. Human factors which contribute to crashes include high risk behaviours like speeding and drink driving, and neglect of protective behaviours such as helmet wearing and seat belt wearing. Much research has been devoted to the attitudes, beliefs and perceptions which contribute to these behaviours and omissions, in order to develop interventions aimed at increasing safer road use behaviours and thereby reducing crashes. However, less progress has been made in addressing human factors contributing to crashes in developing countries as compared to the many improvements in road environments and vehicle standards, and this is especially true of fatalistic beliefs and behaviours. This is a significant omission, since in different cultures in developing countries there are strong worldviews in which predestination persists as a central idea, i.e. that one's life (and death) and other events have been mapped out and are predetermined. Fatalism refers to a particular way in which people regard the events that occur in their lives, usually expressed as a belief that an individual does not have personal control over circumstances and that their lives are determined through a divine or powerful external agency (Hazen & Ehiri, 2006). These views are at odds with the dominant themes of modern health promotion movements, and present significant challenges for health advocates who aim to avert road crashes and diminish their consequences. The limited literature on fatalism reveals that it is not a simple concept, with religion, culture, superstition, experience, education and degree of perceived control of one's life all being implicated in accounts of fatalism. One distinction in the literature that seems promising is the distinction between empirical and theological fatalism, although there are areas of uncertainty about how well-defined the distinction between these types of fatalism is. Research into road safety in Pakistan is scarce, as is the case for other South Asian countries. From the review of the literature conducted, it is clear that the descriptions given of the different belief systems in developing countries including Pakistan are not entirely helpful for health promotion purposes and that further research is warranted on the influence of fatalism, superstition and other related beliefs in road safety. Based on the information available, a conceptual framework is developed as a means of structuring and focusing the research and analysis. The framework is focused on the influence of fatalism, superstition, religion and culture on beliefs about crashes and road user behaviour. Accordingly, this research aims to provide an understanding of the operation of fatalism and related beliefs in Pakistan to assist in the development and implementation of effective and culturally appropriate interventions. The research examines the influence of fatalism, superstition, religious and cultural beliefs on risky road use in Pakistan and is guided by three research questions: 1. What are the perceptions of road crash causation in Pakistan, in particular the role of fatalism, superstition, religious and cultural beliefs? 2. How does fatalism, superstition, and religious and cultural beliefs influence road user behaviour in Pakistan? 3. Do fatalism, superstition, and religious and cultural beliefs work as obstacles to road safety interventions in Pakistan? To address these questions, a qualitative research methodology was developed. The research focused on gathering data through individual in-depth interviewing using a semi-structured interview format. A sample of 30 participants was interviewed in Pakistan in the cities of Lahore, Rawalpindi and Islamabad. The participants included policy makers (with responsibility for traffic law), experienced police officers, religious orators, professional drivers (truck, bus and taxi) and general drivers selected through a combination of purposive, criterion and snowball sampling. The transcripts were translated from Urdu and analysed using a thematic analysis approach guided by the conceptual framework. The findings were divided into four areas: attribution of crash causation to fatalism; attribution of road crashes to beliefs about superstition and malicious acts; beliefs about road crash causation linked to popular concepts of religion; and implications for behaviour, safety and enforcement. Fatalism was almost universally evident, and expressed in a number of ways. Fate was used to rationalise fatal crashes using the argument that the people killed were destined to die that day, one way or another. Related to this was the sense of either not being fully in control of the vehicle, or not needing to take safety precautions, because crashes were predestined anyway. A variety of superstitious-based crash attributions and coping methods to deal with road crashes were also found, such as belief in the role of the evil eye in contributing to road crashes and the use of black magic by rivals or enemies as a crash cause. There were also beliefs related to popular conceptions of religion, such as the role of crashes as a test of life or a source of martyrdom. However, superstitions did not appear to be an alternative to religious beliefs. Fate appeared as the 'default attribution' for a crash when all other explanations failed to account for the incident. This pervasive belief was utilised to justify risky road use behaviour and to resist messages about preventive measures. There was a strong religious underpinning to the statement of fatalistic beliefs (this reflects popular conceptions of Islam rather than scholarly interpretations), but also an overlap with superstitious and other culturally and religious-based beliefs which have longer-standing roots in Pakistani culture. A particular issue which is explored in more detail is the way in which these beliefs and their interpretation within Pakistani society contributed to poor police reporting of crashes. The pervasive nature of fatalistic beliefs in Pakistan affects road user behaviour by supporting continued risk taking behaviour on the road, and by interfering with public health messages about behaviours which would reduce the risk of traffic crashes. The widespread influence of these beliefs on the ways that people respond to traffic crashes and the death of family members contribute to low crash reporting rates and to a system which appears difficult to change. Fate also appeared to be a major contributing factor to non-reporting of road crashes. There also appeared to be a relationship between police enforcement and (lack of) awareness of road rules. It also appears likely that beliefs can influence police work, especially in the case of road crash investigation and the development of strategies. It is anticipated that the findings could be used as a blueprint for the design of interventions aimed at influencing broad-spectrum health attitudes and practices among the communities where fatalism is prevalent. The findings have also identified aspects of beliefs that have complex social implications when designing and piloting driver intervention strategies. By understanding attitudes and behaviours related to fatalism, superstition and other related concepts, it should be possible to improve the education of general road users, such that they are less likely to attribute road crashes to chance, fate, or superstition. This study also underscores the understanding of this issue in high echelons of society (e.g., policy makers, senior police officers) as their role is vital in dispelling road users' misconceptions about the risks of road crashes. The promotion of an evidence or scientifically-based approach to road user behaviour and road safety is recommended, along with improved professional education for police and policy makers.

Intratherapist reliability in the rating of scapula posture in multiple planes of reference

Background: Evaluation of scapular posture is a fundamental component in the clinical evaluation of the upper quadrant. This study examined the intrarater reliability of scapular posture ratings. Methods: A test-retest reliability investigation was undertaken with one week between assessment sessions. At each session physical therapists conducted visual assessments of scapula posture (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane). These five plane ratings were performed for four different scapular posture perturbating conditions (rest, isometric shoulder; flexion, abduction, and external rotation). Results. A total of 100 complete scapular posture ratings (50 left, 50 right) were undertaken at each assessment. The observed agreement between the test and retest postural plane ratings ranged from 59% to 87%; 16 of the 20 plane-condition combinations exceeded 75% observed agreement. Kappa (and prevalence adjusted bias adjusted kappa) values were inconsistent across the postural planes and perturbating conditions. Conclusions: This investigation generally revealed fair to moderate intrarater reliability in the rating of scapular posture by visual inspection. However, enough disagreement between assessments was present to warrant caution when interpreting perceived changes in scapula position between longitudinal assessments using visual inspection alone.

park(ing) day

Walking through the city, passersby are occasionally jolted out of the mundane by surprises that seem out of place or incongruous with the expected urban function––a hidden cafe, or an unknown public art project. If you happen to be wandering through a major city on the third Friday of September each year, you might encounter a parking space that has been temporarily transformed into a "park" with green grass, a bench and an umbrella, perhaps a lemonade stand, a nursery, or an interactive space with a survey about local issues.